Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male W...Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male Wistar albino rats(Rattus norvegicus)weighing 160-200 g and aged 5-6 months randomly received a single intratesticular injection of normal saline(Group A),zinc gluconate 13.3 mg/mL plus L-Arginine(Group B),20%CaCl_(2)(Group C),and CdCl_(2)0.5 mg/kg body weight plus ethylenediaminetetraacetic acid(EDTA)(Group D),respectively,along the entire route from the caudoventral aspect of each testis.They were euthanized up to 180 days to evaluate reproductive tract toxicology.Results:The reproductive organ weights were markedly reduced,with testes severely atrophied in group B,pea-sized and stony hard in group C,and moderately reduced in group D.Azoospermia was evident in groups B and C,while sperm concentration was reduced to<1 million/mL with zero sperm motility in group D.Rats of groups B and C failed to show mounting and copulatory behaviour.A completely disorganized mesh of cellular elements was observed in the seminiferous tubules of group B,while pyknotic germ cell and arrest of spermatogenesis,exfoliated germ cells,occasional syncytial bodies and smaller Leydig cells were evident in groups C and D.Significantly reduced testosterone levels,increased luteinizing hormone(LH)and follicle-stimulating hormone(FSH)levels,returned to normal after 90 days in group D.Conclusions:Zinc gluconate and CaCl_(2)injections severely affected the reproductive organs and libido and rats treated with CdCl_(2)exhibited diminished spermatogenesis with normal libido.Thus,the need-based selection of intratesticular agents should consider their distinct effects on spermatogenesis,libido,and hormonal balance for achieving targeted sterilization outcomes.展开更多
Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplanta...Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplantation of retinal progenitor cells alone.Bone marrow mesenchymal stem cells regulate and interact with various cells in the retinal microenvironment by secreting neurotrophic factors and extracellular vesicles.Small extracellular vesicles derived from bone marrow mesenchymal stem cells,which offer low immunogenicity,minimal tumorigenic risk,and ease of transportation,have been utilized in the treatment of various neurological diseases.These vesicles exhibit various activities,including anti-inflammatory actions,promotion of tissue repair,and immune regulation.Therefore,novel strategies using human retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles may represent an innovation in stem cell therapy for retinal degeneration.In this study,we developed such an approach utilizing retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles to treat retinal degeneration in Royal College of Surgeons rats,a genetic model of retinal degeneration.Our findings revealed that the combination of bone marrow mesenchymal stem cell-derived small extracellular vesicles and retinal progenitor cells significantly improved visual function in these rats.The addition of bone marrow mesenchymal stem cell-derived small extracellular vesicles as adjuvants to stem cell transplantation with retinal progenitor cells enhanced the survival,migration,and differentiation of the exogenous retinal progenitor cells.Concurrently,these small extracellular vesicles inhibited the activation of regional microglia,promoted the migration of transplanted retinal progenitor cells to the inner nuclear layer of the retina,and facilitated their differentiation into photoreceptors and bipolar cells.These findings suggest that bone marrow mesenchymal stem cell-derived small extracellular vesicles potentiate the therapeutic efficacy of retinal progenitor cells in retinal degeneration by promoting their survival and differentiation.展开更多
BACKGROUND Magnetic compression anastomosis(MCA)offers a simple and reliable technique for inducing anastomoses at any point along the digestive tract.Evidence regarding whether the design of the MCA device influences...BACKGROUND Magnetic compression anastomosis(MCA)offers a simple and reliable technique for inducing anastomoses at any point along the digestive tract.Evidence regarding whether the design of the MCA device influences the anastomosis effect is lacking.AIM To investigate any difference in the side-to-side colonic anastomosis effect achieved with cylindrical vs circular ring magnets.METHODS We designed cylindrical and circular ring magnets suitable for side-to-side colonic anastomosis in rats.Thirty Sprague-Dawley rats were randomly divided into a cylindrical group,circular ring group,and cylindrical–circular ring group(n=10/group).Side-to-side colonic anastomosis was completed by transanal insertion of the magnets without incision of the colon.Operation time,perioperative complications,and magnet discharge time were recorded.Rats were euthanized 4 weeks postoperatively,and anastomotic specimens were obtained.The burst pressure and anastomotic diameter were measured sequentially,and anastomosis formation was observed by naked eye.Histological results were observed by light microscopy.RESULTS In all 30 rats,side-to-side colonic anastomosis was completed,for an operation success rate of 100%.No postoperative complications of bleeding and intestinal obstruction occurred,and the postoperative survival rate were 100%.The operation time,magnet discharge time,anastomotic bursting pressure,and anastomotic diameter did not differ significantly among the three designs(P>0.05).Healing was similar across the groups,with gross specimens showing good anastomotic healing and good mucosal continuity observed on histological analysis.CONCLUSION This study found no significant difference in the establishment of rat side-to-side colonic anastomosis with the use of cylindrical vs circular ring magnets.展开更多
Background:Obesity represents a major public health issue,closely linked to a range of metabolic and reproductive disorders.Electroacupuncture(EA)has emerged as a potential non-pharmacological intervention that may al...Background:Obesity represents a major public health issue,closely linked to a range of metabolic and reproductive disorders.Electroacupuncture(EA)has emerged as a potential non-pharmacological intervention that may alleviate complications associated with obesity,including reproductive dysfunction.Objectives:This study sought to evaluate the impact of EA on leptin/kisspeptin signaling pathways and hypothalamic inflammation in obese male rats,with the aim of elucidating its potential mechanisms in mitigating reproductive disorders related to obesity.Methods:Forty male Wistar rats were allocated into two groups:a regular diet(RD,n=10)group and a high-fat diet(HFD,n=30)group.Following an 8-week period,23 out of the 30 rats in the HFD group satisfied the criteria for the obesity model,characterized by a body weight surpassing 20%of the average body weight of the RD group.From these 23 obese rats,20 were randomly selected and further subdivided into the Model(n=10)and EA(n=10)groups.The EA group underwent EA treatment at the Zusanli(ST36),Shenshu(BL23),and Sanyinjiao(SP6)acupoints over a duration of 4 weeks.The study assessed parameters including body weight,serum lipid levels,reproductive hormone levels,hypothalamic histology,inflammation markers,and neurotransmitter levels.Results:EA treatment significantly reduced body weight,improved lipid profiles,and restored hormone levels towards those seen in control animals.Histological analysis showed improved neuronal integrity and a shift in microglial polarization towards an anti-inflammatory phenotype in the EA group.EA treatment was associated with improvements in leptin and kisspeptin signaling activity,which may contribute to its beneficial effects on reproductive function in obese male rats.Neurotransmitter profiling and untargeted serum metabolomics revealed significant improvements in metabolic pathways related to amino acid and lipid metabolism,including key pathways associated with dopamine,serotonin,and glutamine.Conclusions:EA significantly alleviated obesity-induced reproductive dysfunction by modulating leptin and kisspeptin signaling,reducing hypothalamic inflammation,and improving neurotransmitter and serum metabolic profiles,suggesting its potential as a therapeutic strategy for reproductive issues related to obesity.Additional research is essential to investigate the molecular pathways of EA and assess its clinical applicability.展开更多
Infants exhibit diminished susceptibility to external infections,a phenomenon closely linked to the pervasive presence of the bifidobacterial community within their intestinal tract.Nonetheless,a significant knowledge...Infants exhibit diminished susceptibility to external infections,a phenomenon closely linked to the pervasive presence of the bifidobacterial community within their intestinal tract.Nonetheless,a significant knowledge gap remains concerning the distinct species of bifidobacteria initiating anti-infection immune responses during the early developmental stages.In this study,the impact of early intervention with Bifidobacterium bifidum,Bifidobacterium breve,and Bifidobacterium longum on neonatal rats infected with Salmonella enterica serovar Typhimurium SL1344 were compared.The study encompasses various immunity levels,including gut immunity,central immunity(thymus),peripheral immunity(spleen),and brain immunity.Following Salmonella infection,significant alterations in neonatal rats were observed in growth and developmental levels,immune markers,cytokine levels,balance of T lymphocyte subpopulations,intestinal barrier function,and blood-brain barrier integrity.Compared with B.breve and B.longum,B.bifidum demonstrated more pronounced efficacy in regulating these physiological processes.By conducting multi-level analyses of gut microbiota,bifidobacterial community,colonic content metabolomics,and serum metabolomics,the significance of B.bifidum’s role is underscored,and the immune-enhancing function of messenger metabolites is unveiled.Among these metabolites,γ-L-glutamyl-L-glutamic acid and orotic acid were found to be shared by all 3 species,while hippuric acid and 1a,1b-dihomo prostaglandin F2αwere unique to B.bifidum,and DL-arginine was specific to B.longum.Overall,this study has provided novel insights into the intervention and immunomodulation by Bifidobacterium in early-life infections,emphasizing the significant role of B.bifidum.展开更多
This study aimed to assess the therapeutic potential of Anemarrhenae Rhizoma(AR)in osteoporotic rats and to elucidate the metabolic pathways involved in AR’s role in alleviating osteoporosis(OP).OP was induced in rat...This study aimed to assess the therapeutic potential of Anemarrhenae Rhizoma(AR)in osteoporotic rats and to elucidate the metabolic pathways involved in AR’s role in alleviating osteoporosis(OP).OP was induced in rats through ovariectomy(OVX),followed by oral administration of either high or low doses of AR,as well as estradiol valerate,over a 14-week period.Micro-computed tomography(Micro-CT)was employed to examine the femur tissue morphology,while enzyme-linked immunosorbent assay(ELISA)was adopted to measure serum levels of PINP and CTX-I to evaluate AR’s efficacy in treating OP.Additionally,metabolomic profiling of femur tissues was conducted using gas chromatography-mass spectrometry(GC-MS).The bioactive components of AR,along with its therapeutic targets for OP,were identified through UPLC-MS/MS and online database searches,and metabolic networks were established by integrating differential metabolites and potential targets.Furthermore,Western blotting analysis confirmed key molecular targets.The findings revealed that AR treatment significantly mitigated OVX-induced OP in rats.Metabolomic analysis indicated that AR exerted its effects by modulating the levels of 10 key metabolites(such as linoleic acid and inositol)and influencing five crucial metabolic pathways,including linoleic acid metabolism and the phosphoinositide signaling system.Among these,the linoleic acid metabolic pathway emerged as a pivotal focus for further investigation based on the constructed interaction network of differential metabolites and targets.Western blotting analysis demonstrated that AR reversed the up-regulation of CYP1A2 and CYP2C9,two targets associated with the linoleic acid metabolic pathwa y,in OP rats.In conclusion,AR appeared to ameliorate OP by modulating metabolite levels in OVX rats,with its mechanism of action likely centered on regulating the linoleic acid metabolic pathway.展开更多
The prevalence of iron deficiency anemia(IDA)remains high in infants,resulting in growth retardation,neurodevelopmental impairment,immunodeficiency and other irreversible injuries.Efficient and safe iron supplementati...The prevalence of iron deficiency anemia(IDA)remains high in infants,resulting in growth retardation,neurodevelopmental impairment,immunodeficiency and other irreversible injuries.Efficient and safe iron supplementation for infants has been the goal of recent research.This study aims to investigate the effect of encapsulated ferric pyrophosphate(FePP)on intestinal inflammation and gut microbiota in IDA suckling rats.Newborn Sprague-Dawley rats were gavaged with low and high doses of FePP and FeSO4(2 and 10 mg Fe/kg BW,respectively)during postnatal days 2-14,while the Ctrl group was gavaged with saline.Results showed that FePP supplementation was as effective as FeSO4 in promoting growth,alleviating anemia and restoring body iron levels.Both low and high doses of FePP could significantly down-regulate the expression of pro inflammatory cytokines in the colon to the level similar to that in the Ctrl group(P>0.05).However,the high dose of FeSO4 did not show a down-regulation effect.Compared with the Ctrl group,IDA caused a disturbance of gut microbiota composition in suckling rats,and FePP could restore this dysbiosis.Besides,FePP was more beneficial than FeSO4 in increasing the abundance of beneficial bacteria such as Bacteroides and Akkermansia.Spearman’s correlation analysis showed a correlation between gut microbiota and biochemical indicators such as iron status,pro-inflammatory cytokine expression,and oxidative stress level.Overall,these findings suggested that FePP could effectively improve IDA,and is more effective than FeSO4 in alleviating intestinal inflammation and regulating gut microbiota,which provides a basis for the application of new iron fortificant in infant formula.展开更多
Humans and animals have a fundamental ability to use experiences and environmental information to organize behavior.It often happens that humans and animals make decisions and prepare actions under uncertain situation...Humans and animals have a fundamental ability to use experiences and environmental information to organize behavior.It often happens that humans and animals make decisions and prepare actions under uncertain situations.Uncertainty would significantly affect the state of animals’minds,but may not be reflected in behavior.How to“read animals’mind state”under different situations is a challenge.Here,we report that neuronal activity in the medial prefrontal cortex(mPFC)of rats can reflect the environmental uncertainty when the task situation changes from certain to uncertain.Rats were trained to perform behavioral tasks under certain and uncertain situations.Under certain situations,rats were required to simply repeat two nose-poking actions that each triggered short auditory tone feedback(single-task situation).Whereas under the uncertain situation,the feedback could randomly be either the previous tone or a short musical rhythm.No additional action was required upon the music feedback,and the same secondary nose-poking action was required upon the tone feedback(dual-task situation);therefore,the coming task was uncertain before action initiation.We recorded single-unit activity from the mPFC when the rats were performing the tasks.We found that in the dual task,when uncertainty was introduced,many mPFC neurons were actively engaged in dealing with the uncertainty before the task initiation,suggesting that the rats could be aware of the task situation change and encode the information in the mPFC before the action of task initiation.展开更多
AIM:To investigate the functions and potential mechanisms of obtusifolin in dry eye disease(DED)in a rat model.METHODS:A rat DED model was established via topical administration of benzalkonium chloride(BAC),followed ...AIM:To investigate the functions and potential mechanisms of obtusifolin in dry eye disease(DED)in a rat model.METHODS:A rat DED model was established via topical administration of benzalkonium chloride(BAC),followed by administration of obtusifolin.Conjunctival irritation score and tear production were measured to evaluate DED symptoms.Enzyme-linked immunosorbent assay(ELISA)was employed for determining inflammatory cytokine levels in rat conjunctiva.Periodic acid-Schiff staining and corneal fluorescein staining were implemented for assessing goblet cell numbers and corneal epithelial defects,respectively.Western blotting showed zonula occludens-1(ZO-1),matrix metalloproteinase-9(MMP-9),and mitogen-activated protein kinase(MAPK)/nuclear factor kappa B(NF-κB)signaling-related protein levels in the conjunctiva.RESULTS:Topical application of obtusifolin alleviated conjunctival irritation and enhanced tear production in BAC-induced DED rats.Obtusifolin attenuated conjunctival inflammatory response and goblet cell loss as well as corneal epithelial barrier disruption in DED rats.Obtusifolin suppressed extracellular signal-regulated kinase(ERK),p38,and NF-κB phosphorylation in the conjunctiva of DED rats.CONCLUSION:Obtusifolin ameliorates DED in rats possibly by alleviating inflammation via the inactivation of MAPK/NF-κB signaling.展开更多
BACKGROUND Insomnia is closely associated with anxiety and depression,with its pathogenesis involving biological,psychological,and social factors.Sini powder and Suanzaoren decoction are clinically effective tradition...BACKGROUND Insomnia is closely associated with anxiety and depression,with its pathogenesis involving biological,psychological,and social factors.Sini powder and Suanzaoren decoction are clinically effective traditional Chinese medicine formulas for insomnia,demonstrating promising bioactivity.However,the capability of the active components of Sini-Suanzaoren decoction(SNSZRD)to cross the bloodbrain barrier(BBB)and their precise molecular mechanisms,particularly concerning the MT-SIRT1 pathway and mitochondrial function,remain largely unexplored.AIM To elucidate the bioactive components of SNSZRD that are capable of BBB penetration and investigate the therapeutic mechanism of SNSZRD against insomnia.METHODS The chemical components of SNSZRD were analyzed through liquid chromatography-mass spectrometry(LC-MS).Male Sprague-Dawley rats were intraperitoneally injected with DL-4-chlorophenylalanine(PCPA)to establish an insomnia model.Rats were divided into control,model,eszopiclone(positive control),and SNSZRD low-/medium-/high-dose groups.Molecular docking predicted BBBpenetrating components and their binding affinity for SIRT1.Key pathways were analyzed through open-field tests,elevated plus-maze tests,pentobarbital-induced sleep experiments,Haematoxylin and eosin staining,Nissl staining,ELISA,Western blot analysis,quantitative real-time PCR,and immunohistochemistry.RESULTS LC-MS identified 1574 compounds in SNSZRD,of which eight prototype components(e.g.,pachymic acid and senkyunolide G)could cross the BBB.Molecular docking revealed that these components formed stable hydrogen bonds with the SIRT1 protein.SNSZRD treatment significantly ameliorated PCPA-induced anxiety-like behaviors and sleep latency/sleep duration,as well as reduced neuronal degeneration and Nissl body loss in the hypothalamus of treated rats.Additionally,SNSZRD elevated serum melatonin and hypothalamus ATP levels and upregulated the mRNA and protein expression levels of arylalkylamine N-acetyltransferase,SIRT1,PPARγcoactivator-1α,nuclear respiratory factor-1,and mitochondrial transcription factor A in the MT-SIRT1-mitochondrial biogenesis pathway.CONCLUSION SNSZRD might exert its therapeutic effects on insomnia by modulating MT-SIRT1 axis-regulated mitochondrial biogenesis in rats and might serve as an effective therapeutic agent for insomnia.展开更多
[Objectives]To investigate the effect of extract A from Blumea megacephala(Randeria)Chang et Tseng on the hemostasis of postpartum uterine hemorrhage in early pregnancy rats.[Methods]12 mg/kg of mifepristone and 120μ...[Objectives]To investigate the effect of extract A from Blumea megacephala(Randeria)Chang et Tseng on the hemostasis of postpartum uterine hemorrhage in early pregnancy rats.[Methods]12 mg/kg of mifepristone and 120μg/kg of misoprostol were used to establish the uterine bleeding model of early pregnancy rats,and the effects of the drugs on the amount of uterine bleeding,the contents of angiotensin II(Ang-II)and prostaglandin E 2(PGE 2)in serum,the four factors of coagulation,platelet adhesion,platelet aggregation and platelet number were investigated.[Results]Extract A can shorten prothrombin time(PT)and activated partial thromboplastin time(APTT)in rats.It can reduce the amount of uterine bleeding in the model,reduce the contents of PGE 2 and Ang-II,reduce APTT and PT,increase the content of fibrinogen FIB,enhance platelet adhesion,enhance platelet aggregation and increase the number of platelets.[Conclusions]Extract A has obvious hemostatic effect on uterine bleeding model of early pregnancy rats.It may play a hemostatic role by affecting vasoconstriction-dilation,coagulation factors in the blood s internal and external coagulation system,platelet adhesion and aggregation,increasing FIB content,increasing platelet number,affecting uterine bleeding,etc.,showing the characteristics of multiple pathways and multiple targets.展开更多
Objective To investigate the effects of Zuogui Jiangtang Yishen Formula(左归降糖益肾方,ZGJTYSF)in regulating the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/caspase-1/gasdermin D(GSDMD)sig...Objective To investigate the effects of Zuogui Jiangtang Yishen Formula(左归降糖益肾方,ZGJTYSF)in regulating the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/caspase-1/gasdermin D(GSDMD)signaling axis on pyroptosis in rats with diabetic kidney disease(DKD).Methods Fifty male specific pathogen-free(SPF)grade Goto-Kakizaki(GK)rats(12 weeks old)were fed a high-fat diet for one month to establish an early DKD model.Model establishment was confirmed when fasting blood glucose(FBG)≥11.1 mmol/L and urinary albuminto-creatinine ratio(uACR)≥30 mg/g.The successfully modeled early DKD rats were randomly divided by random number table into five groups(n=10 per group):model group;dapagliflozin group(1.0 mg/kg,by gavage,served as positive control);and low-,medium-,and high-dose of ZGJTYSF groups(4.9,9.9,and 19.9 g/kg,respectively,by gavage).Age-matched male SPF Wistar rats(n=10)served as control group.Rats in control and model groups were gavaged with equivalent volumes of distilled water.Treatment lasted 12 weeks.Changes in uACR,FBG,and renal function were observed in all groups.Hematoxylin-eosin(HE),periodic acid-Schiff(PAS),and Masson staining were used to observe renal histopathological changes.Immunohistochemistry was performed to detect the localization and expression of caspase-1,GSDMD,and NLRP3 in rat renal tissues.Terminal deoxynucleotidyl transferase deoxyuridine triphosphate(dUTP)nick end labeling(TUNEL)was utilized to detect pyroptosis in renal tissues.Quantitative real-time polymerase chain reaction(qPCR)and Western blot were applied to detect mRNA and protein expression levels of NLRP3,caspase-1,GSDMD,interleukin(IL)-1β,and IL-18.Results Compared with model group,all doses of ZGJTYSF showed reductions in FBG,with medium-and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12(P<0.05).For uACR,all doses of ZGJTYSF groups exhibited a decreasing trend,with high-dose of ZGJTYSF group being significantly lower than low-and medium-dose of ZGJTYSF groups at week 12(P<0.05)and showing no significant difference from dapagliflozin group(P>0.05).No significant differences in renal function parameters(serum creatinine,blood urea nitrogen,and uric acid)were observed among groups(P>0.05).Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group,with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group.Immunohistochemistry demonstrated significantly reduced expression of caspase-1,GSDMD,and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group(P<0.05 or P<0.01),while the differences in low-and medium-dose of ZGJTYSF groups were not statistically significant(P>0.05).TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups(P<0.01),indicating a marked reduction in pyroptotic cells.Molecular analysis revealed that compared with model group,both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3,caspase-1,GSDMD,IL-1β,and IL-18 in renal tissues(P<0.01),while low-and medium-dose of ZGJTYSF groups showed downward trends without statistical significance(P>0.05).Conclusion ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis,thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.展开更多
BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling p...BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.展开更多
The antiepileptic effect of pinellia total alkaloids（PTA） on penicillin（PNC） chronically kindled rats was investigated. We investigated the effects of PTA on Glu,Asp,Gly andγ-aminobutyric acid（GABA） concentrati...The antiepileptic effect of pinellia total alkaloids（PTA） on penicillin（PNC） chronically kindled rats was investigated. We investigated the effects of PTA on Glu,Asp,Gly andγ-aminobutyric acid（GABA） concentrations and the expression level of cerebral GABA_A receptor in hippocampus.The influence of PTA on epilepsy seizure latency and degree in PNC chronically kindled rats were observed.High performance liquid chromatography（HPLC） was adopted to measure the concentrations of Glu, Asp,Gly and GABA in hippocampus. Reverse transcriptase-polymerase chain reaction （RT-PCR） was used to determine the expression of cerebral GABAA receptor mRNA. Compared with normal rats, the levels of GABA and Gly decreased obviously while the level of Glu and Asp increased significantly in model rats. The cerebral GABAA receptor mRNA level was also decreased at the same time. The difference was statistically different compared to the control group. PTA could prolong the latent period of the penicillin induced seizure and weaken the extent of seizure, compared with the model group without PTA treatment. Moreover, PTA increased the level of GABA and the expression level of GABAA receptor, while decreased the level of Glu significantly. However, it had no obvious effect on the level of Gly and Asp. Pre-treatment of PTA can also increase the GABAA receptor mRNA level. In conclusion, PTA could alleviate the PNC chronically kindled rat seizure. It increased the GABA level and the expression of GABAA receptor, and it decreased the Glu concentration.展开更多
Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine ...Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter(PM2.5).Methods Forty eight male Wistar rats were randomly divided into six groups:blank control group(C1),water drip control group(C2),PM2.5 exposed group(P),low-dose NAC treated and PM2.5 exposed group(L),middle-dose NAC treated and PM2.5 exposed group(M),and high-dose NAC treated and PM2.5 exposed group(H).PM2.5 suspension(7.5 mg/kg)was administered tracheally once a week for four times.NAC of 125 mg/kg,250 mg/kg and 500 mg/kg was delivered intragastrically to L,M and H group respectively by gavage(10 ml/kg)for six days before PM2.5 exposure.The histopathological changes and human mucin 5 subtype AC(MUC5AC)content in lung tissue of rats were evaluated.We investigated IL-6 in serum and bronchoalveolar lavage fluid(BALF)by Enzyme-linked immunosorbent assay(ELISA),MUC5AC in lung tissue homogenate by ELISA,glutathione peroxidase(GSH-PX)in serum and BALF by spectrophotometry,and the expression of p-ERK1/2,p-JNK1/2 and p-p38 proteins by Western blot.All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells.Rats receiving NAC treatment showed less histological destruction and mucus secretion.Of P,L,M and H group,MUC5AC in lung tissue,IL-6 in serum and BALF were higher than controls(C1 and C2)(all P<0.05),with the highest levels found in the P group and a decreasing trend with increase of NAC dose.The activity of GSH-PX in serum and BALF of PM2.5 exposed rats(P,L,M and H)was lower than that of controls(all P<0.05),with higher activities found in NAC treated rats(L,M,and H),and an increasing trend with increase of NAC dose.The expressions of p-ERK1/2,p-JNK1/2 and p-p38 proteins in PM2.5 exposed lung tissue(P,L,M and H)was higher than controls(all P<0.05),with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation,lung oxidative stress and inflammatory injury induced by PM2.5 in rats.展开更多
Objective To explore the sequential effects of hypoxic exercising on miR-27/PPARγand lipid metabolism targetgene and protein expression levels in the obesity rats’liver.Methods 13-week-old male diet-induced obesity ...Objective To explore the sequential effects of hypoxic exercising on miR-27/PPARγand lipid metabolism targetgene and protein expression levels in the obesity rats’liver.Methods 13-week-old male diet-induced obesity rats were randomlydivided into three groups(n=10):normal oxygen concentration quiet group(N),hypoxia quiet group(H),hypoxic exercise group(HE).Exercise training on the horizontal animal treadmill for 1 h/d,5 d/week for a total of 4 week,and the intensity of horizontaltreadmill training was 20 m/min(hypoxic concentration was 13.6%).Comparison of the weights of perirenal fat and epididymal fat in rats across different groups and calculation of Lee’s index based on body weight and body length of rats in each group were done.And the serum concentrations of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),high-densitylipoprotein cholesterol(HDL-C)levels were detected.RT-PCR and Western Blot were used to detect the levels of miR-27,PPARγ,CYP7A1 and CD36.Results Hypoxic exercise decreased the expression levels of miR-27 in the obese rats’liver,however,theexpression level of PPARγwas gradually increased.The expression levels of miR-27 in HE group were significantly lower than Ngroup(P<0.05).The expression levels of PPARγmRNA in N group were significantly lower than H group(P<0.05),especially lowerthan HE group(P<0.01).The protein expression of PPARγprotein in N group was significantly lower than that other groups(P<0.01).The expression of lipid metabolism-related genes and proteins increased in the obese rats’liver.The expression of CYP7A1mRNA in N group was significantly lower than H group(P<0.05),especially lower than HE group(P<0.01).The expression ofCYP7A1 protein in the obese rats’liver in N group was extremely lower than H group and HE group(P<0.01).The proteinexpression of CD36 in N group was significantly lower than that in HE group(P<0.05).Hypoxia exercise improved the relatedphysiological and biochemical indexes of lipid metabolism disorder.The perirenal fat weight of obese rats in HE group wasextremely lower than N group and H group(P<0.01),and the perirenal fat weight in N group was significantly higher than H group(P<0.05).The epididymal fat weight in N group was significantly higher than H group(P<0.05),and extremely higher than HEgroup(P<0.01).The Lee’s index in HE group was extremely lower than N group and H group(P<0.01).The serum concentration ofTC in obese rats in HE group was extremely lower than N group and H group(P<0.01).The serum concentration of TG in HE groupwas extremely lower than N group and H group(P<0.01).The serum concentration of LDL-C in N group was extremely higher thanHE group(P<0.01).The serum concentration of HDL-C in N group was extremely lower than H group(P<0.01).Conclusion Hypoxiaand hypoxia exercise may negatively regulate the levels of PPARγby inhibiting miR-27 in the obese rats’liver,thereby affecting theexpression of downstream target genes CYP7A1 and CD36,and promoting cholesterol,fatty acid oxidation and HDL-C transport inthe liver,and ultimately the lipid levels in obese rats were improved.The effect of hypoxia exercise on improving blood lipid isbetter than simple hypoxia intervention.展开更多
Objective:To anatomically and phenotypically characterize the insular cortex(IC)-nucleus tractus soli-tari(NTS)neural pathway.Methods:Adult male Sprague-Dawley rats were divided into three experimental cohorts for neu...Objective:To anatomically and phenotypically characterize the insular cortex(IC)-nucleus tractus soli-tari(NTS)neural pathway.Methods:Adult male Sprague-Dawley rats were divided into three experimental cohorts for neural circuit tracing.Anterograde labeling was achieved by injecting anterograde self-complementary adeno-associated viruses(scAAVs)into the IC.Retrograde tracing involved NTS injections of either retrograde scAAVs or FluoroGold(FG),combined with immunofluorescence histochemical staining to identify IC-originating projection neurons.For postsynaptic neurochemical phenotype characterization,IC was injected with AAV2/1-CaMKII-Cre,while a mixture of AAV2/9-Syn-DIO-mCherry and AAV2/9-VGAT1-EGFP was injected into the NTS.The rats were allowed to survive for one week following scAAVs or FG injection or four weeks after recombinase-dependent systems injection.Then the rats were sacrificed,and serial brain sections were prepared for immunofluorescence histochemical staining(brain section containing FG)and subsequent fluorescence/confocal microscopic analysis.Results:(1)Anterograde viral tracing re-vealed dense axonal terminals from the IC projecting to the medial subnucleus of the NTS,while retrograde tracing re-vealed that IC neurons projecting to the NTS were predominantly localized within the dysgranular layer;(2)IC-NTS projection neurons were exclusive glutamatergic(100%,n=3);(3)NTS neurons receiving IC inputs were mainly lo-calized in the medial subnucleus,and were predominantly GABAergic(79.8±3.2%,n=3).Conclusion:The pres-ent results indicate that a descending pathway from excitatory neurons of the IC terminates onto inhibitory neurons of the NTS,which might represent a potential neuromodulatory target for visceral pain disorders.展开更多
Objective To comparatively observe the effect of electroacupuncture at digestive system-related lower he-sea points on the expressions of serum interleukin-1β（IL-1 β）, tumor necrosis factor-α（TNF-α） of colon t...Objective To comparatively observe the effect of electroacupuncture at digestive system-related lower he-sea points on the expressions of serum interleukin-1β（IL-1 β）, tumor necrosis factor-α（TNF-α） of colon tissues and high mobility group box 1 protein（HMGB 1） of ulcerative colitis（UC） model rats, and to explore whether there is relative specificity of electroacupuncture at Shàngjùxū（上巨虚 ST 37）, one of lower he-sea points of large intestine, in treatment of bowel diseases. Method A total of 60 SD rats were randomly divided into control group, model group, ST 37 group, Zúsānl？（足三里 ST 36） group, Xiàjùxū（下巨虚 ST 39） group and Yánglíngquán（阳陵泉 GB 34） group. There were ten rats in each group; five were males, and five were females. UC models were established by clysis with 2, 4, 6-trinitrobenzene sulfonic acid/alcohol solution. After modeling, treatment was conducted for ten days, specimens were collected, colonic ulcers and inflammation were inspected visually and scored. The content of serum IL-1β and the expressions of TNF-α and HMGB 1 in colon were detected through ELISA. Results 1 Compared with control group, the scores of colonic ulcers and inflammation, the content of serum IL-1β and the expressions of TNF-α（except ST 37 group） and HMGB 1 were all higher（P〈0.05, P〈0.01）; 2 compared with model group, the scores of colonic ulcers in ST 36 group and ST 37 group were lower obviously（P〈0.05, P〈0.01）; the expressions of IL-1β, TNF-α and HMGB 1 in the four treatment groups were lower obviously（P〈0.01）; 3 compared with ST 37 group, the expressions of IL-1β, TNF-α and HMGB 1 in other three treatment groups were higher obviously（P〈0.05, P〈0.01）; and the scores of colonic ulcers in ST 39 group and GB 34 group were higher obviously（P〈0.05）. Conclusion 1 The score of colonic ulcers can be reduced through electroacupuncture at ST 37, ST 36, ST 39 and GB 34, which can also reduce the content of serum IL-1β and the expressions of TNF-α and HMGB 1, and effectively inhibit inflammatory response of colon caused by UC; 2 the effect trend of the four acupoints in treatment of UC is： ST 37ST 36ST 39GB 34, and electroacupuncture at ST 37 has the best effect with relative specificity.展开更多
Objective To investigate protective effects of electroacupuncture on injury of lipid peroxidation-induced by liver ischemia in rats with sepsis.Methods Forty-eight male SD rats were subjected to sepsis by cecal ligati...Objective To investigate protective effects of electroacupuncture on injury of lipid peroxidation-induced by liver ischemia in rats with sepsis.Methods Forty-eight male SD rats were subjected to sepsis by cecal ligation and puncture （CLP）,and were randomly divided into a sham operation group （group A）,a CLP model group （group B）,a CLP model plus electroacupuncture （EA） at Zúsānlǐ （足三里 ST 36） group （group C）,a CLP model plus electroacupuncture at a sham acupoint group （group D）,a CLP model with vagotomy group （group E） and a CLP model plus electroacupuncture group after vagotomy （group F）,with 8 rats in each group.CLP was performed after abdominal vagotomy in group E and group F.EA （2 mA,2/100 Hz） was applied at bilateral ＂Zúsānlǐ＂ （足三里 ST 36） in group C and group F,and at sham acupoints in group D,respectively,for 1 hour.The hepatic blood flow （HBF） was detected by a laser-doppler flowmetry at 6 hours after CLP.The activity of plasma alanine transarninase （ALT） was determined;contents of hepatic malondialdehyde （MDA）,activity of xanthine oxidase （XOD） and the rate of water content in the hepati tissue were assessed,respectively.Results Hepatic blood flow was （56.97±11.95） U in group C,which was significantly lower than （80.12± 19.57） U shown in group A,but higher than （42.61±10.97） U in group B,（44.53±9.23） U in group D,（30.05 ±4.46） U in group E and （30.46±6.38） U in group F （all P0.05） at 6 hours after CLP.Meanwhile,the levels of MDA,XOD,ALT and hepatic water content in group C were all significantly higher than those in group A,but lower than those in the other four groups （all P0.05）.The levels of MDA,XOD,ALT and hepatic water content in group E and group F were all significantly higher than those in group D （all P0.05）,while their hepatic blood flow were lower than that in group D （both P0.05）,and no significant differences were found in all the indices mentioned above between group E and group F （all P0.05）.Conclusion Electroacupuncture at ＂Zúsānlǐ＂ （足三里 ST 36） can improve hepatic ischemia,inhibit lipid peroxidation and alleviate hepatic edema and dysfunction in septic rats,which might be related with the completeness of vagus nerves.展开更多
AIM:Microcirculatory disturbances are important early pathophysiological events in various organs during acute pancreatitis.The aim of the study was to evaluate changes in microperfusion of the pancreas,liver,kidney,s...AIM:Microcirculatory disturbances are important early pathophysiological events in various organs during acute pancreatitis.The aim of the study was to evaluate changes in microperfusion of the pancreas,liver,kidney,stomach, colon,skeletal muscle,and to investigate the influence of heparin on the organ microcirculation in caerulein-induced experimental acute pancreatitis. METHODS:Acute pancreatitis was induced by 4 intraperitoneal injections of caerulein(Cn)(15 μg/kg).The organ microcirculation was measured by laser Doppler flowmetry.Serum interleukin 6 and hematocrit levels were analysed. RESULTS:Acute pancreatitis resulted in a significant drop of microperfusion in all examined organs.Heparin administration(2×2.5 mg/kg)improved the microcirculation in pancreas(36.9±4% vs 75.9±10%),liver(56.6±6% vs 75.2±16%),kidney (45.1±6% vs 79.3±5%),stomach (65.2±8% vs 78.1±19%),colon(69.8±6% vs 102.5±19%), and skeletal muscle (59.2±6% vs 77.9±13%).Heparin treatment lowered IL-6(359.0±66 U/mL vs 288.5±58 U/mL) and hematocrit level(53±4% vs 46±3%). CONCLUSION:Heparin administration has a positive influence on organ microcirculatory disturbances accompanying experimental Cn-induced acute pancreatitis.展开更多
基金financially assisted to Timanshi Chansoriya of the fellowship grant of UGC-NFPwD,New Delhi sanctioned vide UGC F.No.01-01/2019-Sch dated 06.11.2020(Serial No.352 ID:NFPWD-2018-20-UTP-6522).
文摘Objective:To investigate the sterilizing potential of zinc gluconate,calcium chloride(CaCl_(2))and cadmium chloride(CdCl_(2))following a single intratesticular administration in adult male rats.Methods:60 adult male Wistar albino rats(Rattus norvegicus)weighing 160-200 g and aged 5-6 months randomly received a single intratesticular injection of normal saline(Group A),zinc gluconate 13.3 mg/mL plus L-Arginine(Group B),20%CaCl_(2)(Group C),and CdCl_(2)0.5 mg/kg body weight plus ethylenediaminetetraacetic acid(EDTA)(Group D),respectively,along the entire route from the caudoventral aspect of each testis.They were euthanized up to 180 days to evaluate reproductive tract toxicology.Results:The reproductive organ weights were markedly reduced,with testes severely atrophied in group B,pea-sized and stony hard in group C,and moderately reduced in group D.Azoospermia was evident in groups B and C,while sperm concentration was reduced to<1 million/mL with zero sperm motility in group D.Rats of groups B and C failed to show mounting and copulatory behaviour.A completely disorganized mesh of cellular elements was observed in the seminiferous tubules of group B,while pyknotic germ cell and arrest of spermatogenesis,exfoliated germ cells,occasional syncytial bodies and smaller Leydig cells were evident in groups C and D.Significantly reduced testosterone levels,increased luteinizing hormone(LH)and follicle-stimulating hormone(FSH)levels,returned to normal after 90 days in group D.Conclusions:Zinc gluconate and CaCl_(2)injections severely affected the reproductive organs and libido and rats treated with CdCl_(2)exhibited diminished spermatogenesis with normal libido.Thus,the need-based selection of intratesticular agents should consider their distinct effects on spermatogenesis,libido,and hormonal balance for achieving targeted sterilization outcomes.
基金supported by the National Natural Science Foundation of China,Nos.82271132(to YL),82101167(to BB)the Natural Science Foundation of Chongqing,Nos.CSTB2022NSCQ-MSX0020(to BB),cstc2019jcyj-msxmX0473(to FC).
文摘Our previous study demonstrated that combined transplantation of bone marrow mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplantation of retinal progenitor cells alone.Bone marrow mesenchymal stem cells regulate and interact with various cells in the retinal microenvironment by secreting neurotrophic factors and extracellular vesicles.Small extracellular vesicles derived from bone marrow mesenchymal stem cells,which offer low immunogenicity,minimal tumorigenic risk,and ease of transportation,have been utilized in the treatment of various neurological diseases.These vesicles exhibit various activities,including anti-inflammatory actions,promotion of tissue repair,and immune regulation.Therefore,novel strategies using human retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles may represent an innovation in stem cell therapy for retinal degeneration.In this study,we developed such an approach utilizing retinal progenitor cells combined with bone marrow mesenchymal stem cell-derived small extracellular vesicles to treat retinal degeneration in Royal College of Surgeons rats,a genetic model of retinal degeneration.Our findings revealed that the combination of bone marrow mesenchymal stem cell-derived small extracellular vesicles and retinal progenitor cells significantly improved visual function in these rats.The addition of bone marrow mesenchymal stem cell-derived small extracellular vesicles as adjuvants to stem cell transplantation with retinal progenitor cells enhanced the survival,migration,and differentiation of the exogenous retinal progenitor cells.Concurrently,these small extracellular vesicles inhibited the activation of regional microglia,promoted the migration of transplanted retinal progenitor cells to the inner nuclear layer of the retina,and facilitated their differentiation into photoreceptors and bipolar cells.These findings suggest that bone marrow mesenchymal stem cell-derived small extracellular vesicles potentiate the therapeutic efficacy of retinal progenitor cells in retinal degeneration by promoting their survival and differentiation.
基金Supported by the Key Research and Development Program of Shaanxi,No.2024SF-YBXM-447the Institutional Foundation of The First Affiliated Hospital of Xi’an Jiaotong University,No.2022MS-07the Fundamental Research Funds for the Central Universities,No.xzy022023068.
文摘BACKGROUND Magnetic compression anastomosis(MCA)offers a simple and reliable technique for inducing anastomoses at any point along the digestive tract.Evidence regarding whether the design of the MCA device influences the anastomosis effect is lacking.AIM To investigate any difference in the side-to-side colonic anastomosis effect achieved with cylindrical vs circular ring magnets.METHODS We designed cylindrical and circular ring magnets suitable for side-to-side colonic anastomosis in rats.Thirty Sprague-Dawley rats were randomly divided into a cylindrical group,circular ring group,and cylindrical–circular ring group(n=10/group).Side-to-side colonic anastomosis was completed by transanal insertion of the magnets without incision of the colon.Operation time,perioperative complications,and magnet discharge time were recorded.Rats were euthanized 4 weeks postoperatively,and anastomotic specimens were obtained.The burst pressure and anastomotic diameter were measured sequentially,and anastomosis formation was observed by naked eye.Histological results were observed by light microscopy.RESULTS In all 30 rats,side-to-side colonic anastomosis was completed,for an operation success rate of 100%.No postoperative complications of bleeding and intestinal obstruction occurred,and the postoperative survival rate were 100%.The operation time,magnet discharge time,anastomotic bursting pressure,and anastomotic diameter did not differ significantly among the three designs(P>0.05).Healing was similar across the groups,with gross specimens showing good anastomotic healing and good mucosal continuity observed on histological analysis.CONCLUSION This study found no significant difference in the establishment of rat side-to-side colonic anastomosis with the use of cylindrical vs circular ring magnets.
基金supported by the Natural Science Foundation of Sichuan Province(2023NSFSC1799)the Science and Technology Development Fund of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine(23YY07)National Natural Science Foundation of China(82405413).
文摘Background:Obesity represents a major public health issue,closely linked to a range of metabolic and reproductive disorders.Electroacupuncture(EA)has emerged as a potential non-pharmacological intervention that may alleviate complications associated with obesity,including reproductive dysfunction.Objectives:This study sought to evaluate the impact of EA on leptin/kisspeptin signaling pathways and hypothalamic inflammation in obese male rats,with the aim of elucidating its potential mechanisms in mitigating reproductive disorders related to obesity.Methods:Forty male Wistar rats were allocated into two groups:a regular diet(RD,n=10)group and a high-fat diet(HFD,n=30)group.Following an 8-week period,23 out of the 30 rats in the HFD group satisfied the criteria for the obesity model,characterized by a body weight surpassing 20%of the average body weight of the RD group.From these 23 obese rats,20 were randomly selected and further subdivided into the Model(n=10)and EA(n=10)groups.The EA group underwent EA treatment at the Zusanli(ST36),Shenshu(BL23),and Sanyinjiao(SP6)acupoints over a duration of 4 weeks.The study assessed parameters including body weight,serum lipid levels,reproductive hormone levels,hypothalamic histology,inflammation markers,and neurotransmitter levels.Results:EA treatment significantly reduced body weight,improved lipid profiles,and restored hormone levels towards those seen in control animals.Histological analysis showed improved neuronal integrity and a shift in microglial polarization towards an anti-inflammatory phenotype in the EA group.EA treatment was associated with improvements in leptin and kisspeptin signaling activity,which may contribute to its beneficial effects on reproductive function in obese male rats.Neurotransmitter profiling and untargeted serum metabolomics revealed significant improvements in metabolic pathways related to amino acid and lipid metabolism,including key pathways associated with dopamine,serotonin,and glutamine.Conclusions:EA significantly alleviated obesity-induced reproductive dysfunction by modulating leptin and kisspeptin signaling,reducing hypothalamic inflammation,and improving neurotransmitter and serum metabolic profiles,suggesting its potential as a therapeutic strategy for reproductive issues related to obesity.Additional research is essential to investigate the molecular pathways of EA and assess its clinical applicability.
基金supported by the National Natural Science Foundation of China(32272332,31972052,32021005,31820103010)the Fundamental Research Funds for the Central Universities(JUSRP622020,JUSRP22006,JUSRP51501)the Program of Collaborative Innovation Centre of Food Safety and Quality Control in Jiangsu Province,Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX22_2391).
文摘Infants exhibit diminished susceptibility to external infections,a phenomenon closely linked to the pervasive presence of the bifidobacterial community within their intestinal tract.Nonetheless,a significant knowledge gap remains concerning the distinct species of bifidobacteria initiating anti-infection immune responses during the early developmental stages.In this study,the impact of early intervention with Bifidobacterium bifidum,Bifidobacterium breve,and Bifidobacterium longum on neonatal rats infected with Salmonella enterica serovar Typhimurium SL1344 were compared.The study encompasses various immunity levels,including gut immunity,central immunity(thymus),peripheral immunity(spleen),and brain immunity.Following Salmonella infection,significant alterations in neonatal rats were observed in growth and developmental levels,immune markers,cytokine levels,balance of T lymphocyte subpopulations,intestinal barrier function,and blood-brain barrier integrity.Compared with B.breve and B.longum,B.bifidum demonstrated more pronounced efficacy in regulating these physiological processes.By conducting multi-level analyses of gut microbiota,bifidobacterial community,colonic content metabolomics,and serum metabolomics,the significance of B.bifidum’s role is underscored,and the immune-enhancing function of messenger metabolites is unveiled.Among these metabolites,γ-L-glutamyl-L-glutamic acid and orotic acid were found to be shared by all 3 species,while hippuric acid and 1a,1b-dihomo prostaglandin F2αwere unique to B.bifidum,and DL-arginine was specific to B.longum.Overall,this study has provided novel insights into the intervention and immunomodulation by Bifidobacterium in early-life infections,emphasizing the significant role of B.bifidum.
基金Foundation items:Wuhan Health Research Fund(Grant No.WZ21A06)National Natural Science Foundation of China(Grant No.81903815)。
文摘This study aimed to assess the therapeutic potential of Anemarrhenae Rhizoma(AR)in osteoporotic rats and to elucidate the metabolic pathways involved in AR’s role in alleviating osteoporosis(OP).OP was induced in rats through ovariectomy(OVX),followed by oral administration of either high or low doses of AR,as well as estradiol valerate,over a 14-week period.Micro-computed tomography(Micro-CT)was employed to examine the femur tissue morphology,while enzyme-linked immunosorbent assay(ELISA)was adopted to measure serum levels of PINP and CTX-I to evaluate AR’s efficacy in treating OP.Additionally,metabolomic profiling of femur tissues was conducted using gas chromatography-mass spectrometry(GC-MS).The bioactive components of AR,along with its therapeutic targets for OP,were identified through UPLC-MS/MS and online database searches,and metabolic networks were established by integrating differential metabolites and potential targets.Furthermore,Western blotting analysis confirmed key molecular targets.The findings revealed that AR treatment significantly mitigated OVX-induced OP in rats.Metabolomic analysis indicated that AR exerted its effects by modulating the levels of 10 key metabolites(such as linoleic acid and inositol)and influencing five crucial metabolic pathways,including linoleic acid metabolism and the phosphoinositide signaling system.Among these,the linoleic acid metabolic pathway emerged as a pivotal focus for further investigation based on the constructed interaction network of differential metabolites and targets.Western blotting analysis demonstrated that AR reversed the up-regulation of CYP1A2 and CYP2C9,two targets associated with the linoleic acid metabolic pathwa y,in OP rats.In conclusion,AR appeared to ameliorate OP by modulating metabolite levels in OVX rats,with its mechanism of action likely centered on regulating the linoleic acid metabolic pathway.
基金funded by the National Natural Science Foundation of China(32001676)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(CAST)(2022QNRC001).
文摘The prevalence of iron deficiency anemia(IDA)remains high in infants,resulting in growth retardation,neurodevelopmental impairment,immunodeficiency and other irreversible injuries.Efficient and safe iron supplementation for infants has been the goal of recent research.This study aims to investigate the effect of encapsulated ferric pyrophosphate(FePP)on intestinal inflammation and gut microbiota in IDA suckling rats.Newborn Sprague-Dawley rats were gavaged with low and high doses of FePP and FeSO4(2 and 10 mg Fe/kg BW,respectively)during postnatal days 2-14,while the Ctrl group was gavaged with saline.Results showed that FePP supplementation was as effective as FeSO4 in promoting growth,alleviating anemia and restoring body iron levels.Both low and high doses of FePP could significantly down-regulate the expression of pro inflammatory cytokines in the colon to the level similar to that in the Ctrl group(P>0.05).However,the high dose of FeSO4 did not show a down-regulation effect.Compared with the Ctrl group,IDA caused a disturbance of gut microbiota composition in suckling rats,and FePP could restore this dysbiosis.Besides,FePP was more beneficial than FeSO4 in increasing the abundance of beneficial bacteria such as Bacteroides and Akkermansia.Spearman’s correlation analysis showed a correlation between gut microbiota and biochemical indicators such as iron status,pro-inflammatory cytokine expression,and oxidative stress level.Overall,these findings suggested that FePP could effectively improve IDA,and is more effective than FeSO4 in alleviating intestinal inflammation and regulating gut microbiota,which provides a basis for the application of new iron fortificant in infant formula.
基金supported by the National Natural Science Foundation of China(32060199,32360197,31971035,and 31771182)the Jiangxi Province Natural Science Foundation(20224ACB206016).
文摘Humans and animals have a fundamental ability to use experiences and environmental information to organize behavior.It often happens that humans and animals make decisions and prepare actions under uncertain situations.Uncertainty would significantly affect the state of animals’minds,but may not be reflected in behavior.How to“read animals’mind state”under different situations is a challenge.Here,we report that neuronal activity in the medial prefrontal cortex(mPFC)of rats can reflect the environmental uncertainty when the task situation changes from certain to uncertain.Rats were trained to perform behavioral tasks under certain and uncertain situations.Under certain situations,rats were required to simply repeat two nose-poking actions that each triggered short auditory tone feedback(single-task situation).Whereas under the uncertain situation,the feedback could randomly be either the previous tone or a short musical rhythm.No additional action was required upon the music feedback,and the same secondary nose-poking action was required upon the tone feedback(dual-task situation);therefore,the coming task was uncertain before action initiation.We recorded single-unit activity from the mPFC when the rats were performing the tasks.We found that in the dual task,when uncertainty was introduced,many mPFC neurons were actively engaged in dealing with the uncertainty before the task initiation,suggesting that the rats could be aware of the task situation change and encode the information in the mPFC before the action of task initiation.
基金Supported by Hubei Provincial Hospital of Traditional Chinese Medicine In-hospital Project(No.2021YJKT-20)Hubei Provincial Administration of Traditional Chinese Medicine,Bureau-level Project(No.ZY2023F008)Hubei Science and Technology Department,General Project(No.2025AFB786).
文摘AIM:To investigate the functions and potential mechanisms of obtusifolin in dry eye disease(DED)in a rat model.METHODS:A rat DED model was established via topical administration of benzalkonium chloride(BAC),followed by administration of obtusifolin.Conjunctival irritation score and tear production were measured to evaluate DED symptoms.Enzyme-linked immunosorbent assay(ELISA)was employed for determining inflammatory cytokine levels in rat conjunctiva.Periodic acid-Schiff staining and corneal fluorescein staining were implemented for assessing goblet cell numbers and corneal epithelial defects,respectively.Western blotting showed zonula occludens-1(ZO-1),matrix metalloproteinase-9(MMP-9),and mitogen-activated protein kinase(MAPK)/nuclear factor kappa B(NF-κB)signaling-related protein levels in the conjunctiva.RESULTS:Topical application of obtusifolin alleviated conjunctival irritation and enhanced tear production in BAC-induced DED rats.Obtusifolin attenuated conjunctival inflammatory response and goblet cell loss as well as corneal epithelial barrier disruption in DED rats.Obtusifolin suppressed extracellular signal-regulated kinase(ERK),p38,and NF-κB phosphorylation in the conjunctiva of DED rats.CONCLUSION:Obtusifolin ameliorates DED in rats possibly by alleviating inflammation via the inactivation of MAPK/NF-κB signaling.
基金Supported by the Beijing Natural Science Foundation,No.7232289.
文摘BACKGROUND Insomnia is closely associated with anxiety and depression,with its pathogenesis involving biological,psychological,and social factors.Sini powder and Suanzaoren decoction are clinically effective traditional Chinese medicine formulas for insomnia,demonstrating promising bioactivity.However,the capability of the active components of Sini-Suanzaoren decoction(SNSZRD)to cross the bloodbrain barrier(BBB)and their precise molecular mechanisms,particularly concerning the MT-SIRT1 pathway and mitochondrial function,remain largely unexplored.AIM To elucidate the bioactive components of SNSZRD that are capable of BBB penetration and investigate the therapeutic mechanism of SNSZRD against insomnia.METHODS The chemical components of SNSZRD were analyzed through liquid chromatography-mass spectrometry(LC-MS).Male Sprague-Dawley rats were intraperitoneally injected with DL-4-chlorophenylalanine(PCPA)to establish an insomnia model.Rats were divided into control,model,eszopiclone(positive control),and SNSZRD low-/medium-/high-dose groups.Molecular docking predicted BBBpenetrating components and their binding affinity for SIRT1.Key pathways were analyzed through open-field tests,elevated plus-maze tests,pentobarbital-induced sleep experiments,Haematoxylin and eosin staining,Nissl staining,ELISA,Western blot analysis,quantitative real-time PCR,and immunohistochemistry.RESULTS LC-MS identified 1574 compounds in SNSZRD,of which eight prototype components(e.g.,pachymic acid and senkyunolide G)could cross the BBB.Molecular docking revealed that these components formed stable hydrogen bonds with the SIRT1 protein.SNSZRD treatment significantly ameliorated PCPA-induced anxiety-like behaviors and sleep latency/sleep duration,as well as reduced neuronal degeneration and Nissl body loss in the hypothalamus of treated rats.Additionally,SNSZRD elevated serum melatonin and hypothalamus ATP levels and upregulated the mRNA and protein expression levels of arylalkylamine N-acetyltransferase,SIRT1,PPARγcoactivator-1α,nuclear respiratory factor-1,and mitochondrial transcription factor A in the MT-SIRT1-mitochondrial biogenesis pathway.CONCLUSION SNSZRD might exert its therapeutic effects on insomnia by modulating MT-SIRT1 axis-regulated mitochondrial biogenesis in rats and might serve as an effective therapeutic agent for insomnia.
基金Supported by the University-level Project of Guangxi University of Chinese Medicine(2021ZD005).
文摘[Objectives]To investigate the effect of extract A from Blumea megacephala(Randeria)Chang et Tseng on the hemostasis of postpartum uterine hemorrhage in early pregnancy rats.[Methods]12 mg/kg of mifepristone and 120μg/kg of misoprostol were used to establish the uterine bleeding model of early pregnancy rats,and the effects of the drugs on the amount of uterine bleeding,the contents of angiotensin II(Ang-II)and prostaglandin E 2(PGE 2)in serum,the four factors of coagulation,platelet adhesion,platelet aggregation and platelet number were investigated.[Results]Extract A can shorten prothrombin time(PT)and activated partial thromboplastin time(APTT)in rats.It can reduce the amount of uterine bleeding in the model,reduce the contents of PGE 2 and Ang-II,reduce APTT and PT,increase the content of fibrinogen FIB,enhance platelet adhesion,enhance platelet aggregation and increase the number of platelets.[Conclusions]Extract A has obvious hemostatic effect on uterine bleeding model of early pregnancy rats.It may play a hemostatic role by affecting vasoconstriction-dilation,coagulation factors in the blood s internal and external coagulation system,platelet adhesion and aggregation,increasing FIB content,increasing platelet number,affecting uterine bleeding,etc.,showing the characteristics of multiple pathways and multiple targets.
基金National Natural Science Foundation of China(U21A20411)Innovative Research Group Program of Hunan Provincial Natural Science Foundation (2024JJ1007)Hunan Provincial Natural Science Foundation(2023JJ30473)。
文摘Objective To investigate the effects of Zuogui Jiangtang Yishen Formula(左归降糖益肾方,ZGJTYSF)in regulating the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/caspase-1/gasdermin D(GSDMD)signaling axis on pyroptosis in rats with diabetic kidney disease(DKD).Methods Fifty male specific pathogen-free(SPF)grade Goto-Kakizaki(GK)rats(12 weeks old)were fed a high-fat diet for one month to establish an early DKD model.Model establishment was confirmed when fasting blood glucose(FBG)≥11.1 mmol/L and urinary albuminto-creatinine ratio(uACR)≥30 mg/g.The successfully modeled early DKD rats were randomly divided by random number table into five groups(n=10 per group):model group;dapagliflozin group(1.0 mg/kg,by gavage,served as positive control);and low-,medium-,and high-dose of ZGJTYSF groups(4.9,9.9,and 19.9 g/kg,respectively,by gavage).Age-matched male SPF Wistar rats(n=10)served as control group.Rats in control and model groups were gavaged with equivalent volumes of distilled water.Treatment lasted 12 weeks.Changes in uACR,FBG,and renal function were observed in all groups.Hematoxylin-eosin(HE),periodic acid-Schiff(PAS),and Masson staining were used to observe renal histopathological changes.Immunohistochemistry was performed to detect the localization and expression of caspase-1,GSDMD,and NLRP3 in rat renal tissues.Terminal deoxynucleotidyl transferase deoxyuridine triphosphate(dUTP)nick end labeling(TUNEL)was utilized to detect pyroptosis in renal tissues.Quantitative real-time polymerase chain reaction(qPCR)and Western blot were applied to detect mRNA and protein expression levels of NLRP3,caspase-1,GSDMD,interleukin(IL)-1β,and IL-18.Results Compared with model group,all doses of ZGJTYSF showed reductions in FBG,with medium-and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12(P<0.05).For uACR,all doses of ZGJTYSF groups exhibited a decreasing trend,with high-dose of ZGJTYSF group being significantly lower than low-and medium-dose of ZGJTYSF groups at week 12(P<0.05)and showing no significant difference from dapagliflozin group(P>0.05).No significant differences in renal function parameters(serum creatinine,blood urea nitrogen,and uric acid)were observed among groups(P>0.05).Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group,with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group.Immunohistochemistry demonstrated significantly reduced expression of caspase-1,GSDMD,and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group(P<0.05 or P<0.01),while the differences in low-and medium-dose of ZGJTYSF groups were not statistically significant(P>0.05).TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups(P<0.01),indicating a marked reduction in pyroptotic cells.Molecular analysis revealed that compared with model group,both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3,caspase-1,GSDMD,IL-1β,and IL-18 in renal tissues(P<0.01),while low-and medium-dose of ZGJTYSF groups showed downward trends without statistical significance(P>0.05).Conclusion ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis,thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.
文摘BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.
基金Natural Science Foundation of Shanxi Province (Grant No.20041109).
文摘The antiepileptic effect of pinellia total alkaloids（PTA） on penicillin（PNC） chronically kindled rats was investigated. We investigated the effects of PTA on Glu,Asp,Gly andγ-aminobutyric acid（GABA） concentrations and the expression level of cerebral GABA_A receptor in hippocampus.The influence of PTA on epilepsy seizure latency and degree in PNC chronically kindled rats were observed.High performance liquid chromatography（HPLC） was adopted to measure the concentrations of Glu, Asp,Gly and GABA in hippocampus. Reverse transcriptase-polymerase chain reaction （RT-PCR） was used to determine the expression of cerebral GABAA receptor mRNA. Compared with normal rats, the levels of GABA and Gly decreased obviously while the level of Glu and Asp increased significantly in model rats. The cerebral GABAA receptor mRNA level was also decreased at the same time. The difference was statistically different compared to the control group. PTA could prolong the latent period of the penicillin induced seizure and weaken the extent of seizure, compared with the model group without PTA treatment. Moreover, PTA increased the level of GABA and the expression level of GABAA receptor, while decreased the level of Glu significantly. However, it had no obvious effect on the level of Gly and Asp. Pre-treatment of PTA can also increase the GABAA receptor mRNA level. In conclusion, PTA could alleviate the PNC chronically kindled rat seizure. It increased the GABA level and the expression of GABAA receptor, and it decreased the Glu concentration.
文摘Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter(PM2.5).Methods Forty eight male Wistar rats were randomly divided into six groups:blank control group(C1),water drip control group(C2),PM2.5 exposed group(P),low-dose NAC treated and PM2.5 exposed group(L),middle-dose NAC treated and PM2.5 exposed group(M),and high-dose NAC treated and PM2.5 exposed group(H).PM2.5 suspension(7.5 mg/kg)was administered tracheally once a week for four times.NAC of 125 mg/kg,250 mg/kg and 500 mg/kg was delivered intragastrically to L,M and H group respectively by gavage(10 ml/kg)for six days before PM2.5 exposure.The histopathological changes and human mucin 5 subtype AC(MUC5AC)content in lung tissue of rats were evaluated.We investigated IL-6 in serum and bronchoalveolar lavage fluid(BALF)by Enzyme-linked immunosorbent assay(ELISA),MUC5AC in lung tissue homogenate by ELISA,glutathione peroxidase(GSH-PX)in serum and BALF by spectrophotometry,and the expression of p-ERK1/2,p-JNK1/2 and p-p38 proteins by Western blot.All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells.Rats receiving NAC treatment showed less histological destruction and mucus secretion.Of P,L,M and H group,MUC5AC in lung tissue,IL-6 in serum and BALF were higher than controls(C1 and C2)(all P<0.05),with the highest levels found in the P group and a decreasing trend with increase of NAC dose.The activity of GSH-PX in serum and BALF of PM2.5 exposed rats(P,L,M and H)was lower than that of controls(all P<0.05),with higher activities found in NAC treated rats(L,M,and H),and an increasing trend with increase of NAC dose.The expressions of p-ERK1/2,p-JNK1/2 and p-p38 proteins in PM2.5 exposed lung tissue(P,L,M and H)was higher than controls(all P<0.05),with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation,lung oxidative stress and inflammatory injury induced by PM2.5 in rats.
文摘Objective To explore the sequential effects of hypoxic exercising on miR-27/PPARγand lipid metabolism targetgene and protein expression levels in the obesity rats’liver.Methods 13-week-old male diet-induced obesity rats were randomlydivided into three groups(n=10):normal oxygen concentration quiet group(N),hypoxia quiet group(H),hypoxic exercise group(HE).Exercise training on the horizontal animal treadmill for 1 h/d,5 d/week for a total of 4 week,and the intensity of horizontaltreadmill training was 20 m/min(hypoxic concentration was 13.6%).Comparison of the weights of perirenal fat and epididymal fat in rats across different groups and calculation of Lee’s index based on body weight and body length of rats in each group were done.And the serum concentrations of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),high-densitylipoprotein cholesterol(HDL-C)levels were detected.RT-PCR and Western Blot were used to detect the levels of miR-27,PPARγ,CYP7A1 and CD36.Results Hypoxic exercise decreased the expression levels of miR-27 in the obese rats’liver,however,theexpression level of PPARγwas gradually increased.The expression levels of miR-27 in HE group were significantly lower than Ngroup(P<0.05).The expression levels of PPARγmRNA in N group were significantly lower than H group(P<0.05),especially lowerthan HE group(P<0.01).The protein expression of PPARγprotein in N group was significantly lower than that other groups(P<0.01).The expression of lipid metabolism-related genes and proteins increased in the obese rats’liver.The expression of CYP7A1mRNA in N group was significantly lower than H group(P<0.05),especially lower than HE group(P<0.01).The expression ofCYP7A1 protein in the obese rats’liver in N group was extremely lower than H group and HE group(P<0.01).The proteinexpression of CD36 in N group was significantly lower than that in HE group(P<0.05).Hypoxia exercise improved the relatedphysiological and biochemical indexes of lipid metabolism disorder.The perirenal fat weight of obese rats in HE group wasextremely lower than N group and H group(P<0.01),and the perirenal fat weight in N group was significantly higher than H group(P<0.05).The epididymal fat weight in N group was significantly higher than H group(P<0.05),and extremely higher than HEgroup(P<0.01).The Lee’s index in HE group was extremely lower than N group and H group(P<0.01).The serum concentration ofTC in obese rats in HE group was extremely lower than N group and H group(P<0.01).The serum concentration of TG in HE groupwas extremely lower than N group and H group(P<0.01).The serum concentration of LDL-C in N group was extremely higher thanHE group(P<0.01).The serum concentration of HDL-C in N group was extremely lower than H group(P<0.01).Conclusion Hypoxiaand hypoxia exercise may negatively regulate the levels of PPARγby inhibiting miR-27 in the obese rats’liver,thereby affecting theexpression of downstream target genes CYP7A1 and CD36,and promoting cholesterol,fatty acid oxidation and HDL-C transport inthe liver,and ultimately the lipid levels in obese rats were improved.The effect of hypoxia exercise on improving blood lipid isbetter than simple hypoxia intervention.
文摘Objective:To anatomically and phenotypically characterize the insular cortex(IC)-nucleus tractus soli-tari(NTS)neural pathway.Methods:Adult male Sprague-Dawley rats were divided into three experimental cohorts for neural circuit tracing.Anterograde labeling was achieved by injecting anterograde self-complementary adeno-associated viruses(scAAVs)into the IC.Retrograde tracing involved NTS injections of either retrograde scAAVs or FluoroGold(FG),combined with immunofluorescence histochemical staining to identify IC-originating projection neurons.For postsynaptic neurochemical phenotype characterization,IC was injected with AAV2/1-CaMKII-Cre,while a mixture of AAV2/9-Syn-DIO-mCherry and AAV2/9-VGAT1-EGFP was injected into the NTS.The rats were allowed to survive for one week following scAAVs or FG injection or four weeks after recombinase-dependent systems injection.Then the rats were sacrificed,and serial brain sections were prepared for immunofluorescence histochemical staining(brain section containing FG)and subsequent fluorescence/confocal microscopic analysis.Results:(1)Anterograde viral tracing re-vealed dense axonal terminals from the IC projecting to the medial subnucleus of the NTS,while retrograde tracing re-vealed that IC neurons projecting to the NTS were predominantly localized within the dysgranular layer;(2)IC-NTS projection neurons were exclusive glutamatergic(100%,n=3);(3)NTS neurons receiving IC inputs were mainly lo-calized in the medial subnucleus,and were predominantly GABAergic(79.8±3.2%,n=3).Conclusion:The pres-ent results indicate that a descending pathway from excitatory neurons of the IC terminates onto inhibitory neurons of the NTS,which might represent a potential neuromodulatory target for visceral pain disorders.
基金Supported by National Natural Science Foundation of China:81173327/H2718
文摘Objective To comparatively observe the effect of electroacupuncture at digestive system-related lower he-sea points on the expressions of serum interleukin-1β（IL-1 β）, tumor necrosis factor-α（TNF-α） of colon tissues and high mobility group box 1 protein（HMGB 1） of ulcerative colitis（UC） model rats, and to explore whether there is relative specificity of electroacupuncture at Shàngjùxū（上巨虚 ST 37）, one of lower he-sea points of large intestine, in treatment of bowel diseases. Method A total of 60 SD rats were randomly divided into control group, model group, ST 37 group, Zúsānl？（足三里 ST 36） group, Xiàjùxū（下巨虚 ST 39） group and Yánglíngquán（阳陵泉 GB 34） group. There were ten rats in each group; five were males, and five were females. UC models were established by clysis with 2, 4, 6-trinitrobenzene sulfonic acid/alcohol solution. After modeling, treatment was conducted for ten days, specimens were collected, colonic ulcers and inflammation were inspected visually and scored. The content of serum IL-1β and the expressions of TNF-α and HMGB 1 in colon were detected through ELISA. Results 1 Compared with control group, the scores of colonic ulcers and inflammation, the content of serum IL-1β and the expressions of TNF-α（except ST 37 group） and HMGB 1 were all higher（P〈0.05, P〈0.01）; 2 compared with model group, the scores of colonic ulcers in ST 36 group and ST 37 group were lower obviously（P〈0.05, P〈0.01）; the expressions of IL-1β, TNF-α and HMGB 1 in the four treatment groups were lower obviously（P〈0.01）; 3 compared with ST 37 group, the expressions of IL-1β, TNF-α and HMGB 1 in other three treatment groups were higher obviously（P〈0.05, P〈0.01）; and the scores of colonic ulcers in ST 39 group and GB 34 group were higher obviously（P〈0.05）. Conclusion 1 The score of colonic ulcers can be reduced through electroacupuncture at ST 37, ST 36, ST 39 and GB 34, which can also reduce the content of serum IL-1β and the expressions of TNF-α and HMGB 1, and effectively inhibit inflammatory response of colon caused by UC; 2 the effect trend of the four acupoints in treatment of UC is： ST 37ST 36ST 39GB 34, and electroacupuncture at ST 37 has the best effect with relative specificity.
基金Supported by State Natural Sciences Foundation(NCFS):30672725Army Medical Health"11th Five-Year Plan"Special Subject:06Z055
文摘Objective To investigate protective effects of electroacupuncture on injury of lipid peroxidation-induced by liver ischemia in rats with sepsis.Methods Forty-eight male SD rats were subjected to sepsis by cecal ligation and puncture （CLP）,and were randomly divided into a sham operation group （group A）,a CLP model group （group B）,a CLP model plus electroacupuncture （EA） at Zúsānlǐ （足三里 ST 36） group （group C）,a CLP model plus electroacupuncture at a sham acupoint group （group D）,a CLP model with vagotomy group （group E） and a CLP model plus electroacupuncture group after vagotomy （group F）,with 8 rats in each group.CLP was performed after abdominal vagotomy in group E and group F.EA （2 mA,2/100 Hz） was applied at bilateral ＂Zúsānlǐ＂ （足三里 ST 36） in group C and group F,and at sham acupoints in group D,respectively,for 1 hour.The hepatic blood flow （HBF） was detected by a laser-doppler flowmetry at 6 hours after CLP.The activity of plasma alanine transarninase （ALT） was determined;contents of hepatic malondialdehyde （MDA）,activity of xanthine oxidase （XOD） and the rate of water content in the hepati tissue were assessed,respectively.Results Hepatic blood flow was （56.97±11.95） U in group C,which was significantly lower than （80.12± 19.57） U shown in group A,but higher than （42.61±10.97） U in group B,（44.53±9.23） U in group D,（30.05 ±4.46） U in group E and （30.46±6.38） U in group F （all P0.05） at 6 hours after CLP.Meanwhile,the levels of MDA,XOD,ALT and hepatic water content in group C were all significantly higher than those in group A,but lower than those in the other four groups （all P0.05）.The levels of MDA,XOD,ALT and hepatic water content in group E and group F were all significantly higher than those in group D （all P0.05）,while their hepatic blood flow were lower than that in group D （both P0.05）,and no significant differences were found in all the indices mentioned above between group E and group F （all P0.05）.Conclusion Electroacupuncture at ＂Zúsānlǐ＂ （足三里 ST 36） can improve hepatic ischemia,inhibit lipid peroxidation and alleviate hepatic edema and dysfunction in septic rats,which might be related with the completeness of vagus nerves.
基金Supported by Medical University of Gda■sk,grant W-120,Poland
文摘AIM:Microcirculatory disturbances are important early pathophysiological events in various organs during acute pancreatitis.The aim of the study was to evaluate changes in microperfusion of the pancreas,liver,kidney,stomach, colon,skeletal muscle,and to investigate the influence of heparin on the organ microcirculation in caerulein-induced experimental acute pancreatitis. METHODS:Acute pancreatitis was induced by 4 intraperitoneal injections of caerulein(Cn)(15 μg/kg).The organ microcirculation was measured by laser Doppler flowmetry.Serum interleukin 6 and hematocrit levels were analysed. RESULTS:Acute pancreatitis resulted in a significant drop of microperfusion in all examined organs.Heparin administration(2×2.5 mg/kg)improved the microcirculation in pancreas(36.9±4% vs 75.9±10%),liver(56.6±6% vs 75.2±16%),kidney (45.1±6% vs 79.3±5%),stomach (65.2±8% vs 78.1±19%),colon(69.8±6% vs 102.5±19%), and skeletal muscle (59.2±6% vs 77.9±13%).Heparin treatment lowered IL-6(359.0±66 U/mL vs 288.5±58 U/mL) and hematocrit level(53±4% vs 46±3%). CONCLUSION:Heparin administration has a positive influence on organ microcirculatory disturbances accompanying experimental Cn-induced acute pancreatitis.
