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
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
Vine tea is documented in ancient Chinese books as having the function of promoting blood circulation.However,its effects and mechanisms remain unclear.The aim of this study was to comprehensively investigate the prot...Vine tea is documented in ancient Chinese books as having the function of promoting blood circulation.However,its effects and mechanisms remain unclear.The aim of this study was to comprehensively investigate the protective potential and mechanisms of vine tea in high-fat diet rat through a combination of in vivo and in vitro experiments.The efficacy of vine tea was evaluated using a high-fat diet rat model and an oxidized low-density lipoprotein-treated cell model,with physiological and biochemical indicators measured in rat serum and cell supernatants.Transcriptomics was utilized to investigate alterations mRNA expression following the administration of dihydromyricetin in cell model.Metabolomics and 16S rRNA sequencing was employed to examine changes in metabolites in the serum and changes in gut microbiota of high-fat diet rats after administering vine tea extract.Vine tea extract and dihydromyricetin can reduce elevated levels of lipids,including total cholesterol and triglycerides,following modeling.Transcriptomic data indicate that dihydromyricetin exerts its effects by regulating ferroptosis signaling pathways.Metabolomic analysis demonstrates that the administration of vine tea extract influences the vitamin K cycle and glutathione,thereby alleviating the progression of ferroptosis.Additionally,16S rRNA sequencing reveals that vine tea extract increases Lactobacillaceae in the gut microbiota,which subsequently affects the levels of lysophosphatidylcholine,a major phospholipid component of oxidized low-density lipoprotein in serum.Our results indicate that vine tea can regulate ferroptosis signaling pathways and increase Lactobacillaceae in the gut microbiota,thereby exhibiting cardiovascular protective effects in high-fat diet rats.展开更多
Stroke induces profound neuroinflammation and systemic immune dysregulation,including disturbances in gut homeostasis.Experimental evidence suggests that intestinal barrier permeability(IBP)and bacterial translocation...Stroke induces profound neuroinflammation and systemic immune dysregulation,including disturbances in gut homeostasis.Experimental evidence suggests that intestinal barrier permeability(IBP)and bacterial translocation(BT)critically influence stroke outcomes.However,biological variability among commonly used rodent substrains has received limited attention.In this pilot study,we compared poststroke immune responses in two Wistar rat substrains obtained from different suppliers:RccHan(Envigo)and RjHan(Janvier).Naive animals(n=4)and rats subjected to permanent cerebral ischemia(n=8 per substrain)were evaluated 72 h after middle cerebral artery occlusion and stratified according to the presence or absence of BT.Immune cell populations in blood and bone marrow were analyzed using flow cytometry,and leukocyte infiltration into ischemic brain tissue was quantified using immunohisto-chemistry.Differences were considered statistically significant when p<0.05.Both substrains developed significant infarcts and neurological deficits.RccHan rats exhibited larger infarct volumes and more extensive BT across multiple organs.In contrast,RjHan rats exhibited BT mainly confined to mesenteric lymph nodes but exhibited greater IBP.Although dissemination was broader in RccHan rats,overall bacterial burden was slightly lower compared with RjHan,and extraintestinal bacterial composition differed between groups.Particularly,RjHan rats exhibited stronger systemic and central immune activation,with significant alterations in lymphocyte and monocyte populations and enhanced granulocyte and T-cell infiltration within ischemic lesions.These findings demonstrate that substrain origin profoundly influences poststroke intestinal barrier integrity,bacterial dissemination,and immune responses considering substrain-related variability is essential to improve reproducibility and translational relevance in preclinical stroke research.展开更多
AIM:To investigate the effects of zingerone(ZO)on the retina in diabetic rats.METHODS:A total of 70 rats were randomly selected and divided into seven groups[diabetic group(Dm+;n=10),diabetic+metformin group(Dm+Met;n=...AIM:To investigate the effects of zingerone(ZO)on the retina in diabetic rats.METHODS:A total of 70 rats were randomly selected and divided into seven groups[diabetic group(Dm+;n=10),diabetic+metformin group(Dm+Met;n=10),diabetic+ZO25 group(Dm+ZO25;n=10),diabetic+ZO50 group(Dm+ZO50;n=10),diabetic+metformin group+ZO 50 Group(Dm+Met+ZO50;n=10)].Diabetes was induced by streptozotocin(STZ),and metformin and two different doses of ZO were administered via gavage.Retinal tissues were evaluated by histopathological and immunohistochemical analyses.RESULTS:In diabetic rats,severe retinal inflammation,tissue necrosis,and increased tumor necrosis factor-α(TNF-α)expression were observed.ZO administration reduced these effects in a dose-dependent manner.Protective effects of metformin alone were limited,and no synergistic benefit was observed in ZO+Met groups.Administration of 50 mg/kg ZO to non-diabetic rats caused no retinal toxicity.Additionally,elevated 8-OHdG and c-Jun N-terminal kinase(JNK)expressions in diabetic retinopathy models were significantly reduced by ZO treatment.CONCLUSION:ZO can markedly reduce the pathological effects of the retina in a diabetic rat model.展开更多
AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided...AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided into four equal groups(n=6/group)as follows:healthy group(HG),ATP-only group(ATPG),sildenafil-onlygroup(SILG),and ATP+sildenafil group(ATP+SLD).ATPG andATP+SLD groups were injected intraperitoneally with ATP(4 mg/kg),while SILG and HG groups were injected withsaline(0.9%NaCl)by the same route as a solvent.One hourafter the administration of ATP and solvent,sildenafil(10 m g/k g)was administered orally to the SILG andATP+SLD groups.This procedure was repeated once a dayfor 4wk.The animals were then sacrificed,eyeballs wereremoved and oxidant and antioxidant parameters weremeasured biochemically.Additionally,the ocular tissueswere evaluated histopathologically.RESULTS:Sildenafil increased oxidant(malondialdehyde)levels and decreased antioxidant levels(total glutathione,superoxide dismutase,catalase)in rat ocular tissues andcaused severe oxidative stress.In addition,sildenafil hasbeen shown histopathologically to cause oxidative damagein retinal layers.ATP treatment suppressed oxidative stressand attenuated histopathological damage in the retinal layers.CONCLUSION:ATP protects retinal tissue againstsildenafil-induced ocular oxidative damage in rats andmay contribute to the development of novel approaches toprevent or treat this damage.展开更多
Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established a...Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established an omohyoid muscle-based PNS rat model combined with MV.Bilateral nerves were exposed within 20±2 min by transection at the intermediate tendon of omohyoid muscle,minimizing trauma and bleeding.Threshold stimulation(0.6±0.2 mA)correlated with body weight.Ventilator-synchronized stimulation increased compound muscle action potentials by~30%,whereas histology confirmed intact nerve.Physiological parameters remained stable throughout ventilation.This model provides a safe and scalable platform for mechanistic and preclinical studies on PNS-mediated protection against MV-induced organ injury.展开更多
Objective:To investigate the mechanism of fire needling in improving autophagy and oxidative stress in rats with cervical spondylosis of vertebral artery type(CSA)by regulating protein kinase B(PKB/Akt)/mammalian targ...Objective:To investigate the mechanism of fire needling in improving autophagy and oxidative stress in rats with cervical spondylosis of vertebral artery type(CSA)by regulating protein kinase B(PKB/Akt)/mammalian target of rapamycin(mTOR)signaling pathway.Methods:The rats were randomly divided into a sham-operation group(Sham group)and a model group.After successful modeling,the rats were randomly divided into a CSA group,a fire needling group,and a fire needling+insulin-like growth factor 1(IGF-1)group.No intervention was performed in the Sham and CSA groups;the fire needling group received fire needling intervention;the fire needling+IGF-1 group received both fire needling and intraperitoneal injection of IGF-1 solution intervention.The inclined plate test was used to detect the exercise ability of rats.Laser Doppler was used to detect the blood flow in the pia mater microcirculation.Multi-mode high-frequency acoustic was used to detect the blood flow velocity of both sides of the vertebral artery.The serum levels of endothelin-1(ET-1),nitric oxide(NO),superoxide dismutase(SOD),and malondialdehyde(MDA)were measured.A transmission electron microscope was used to observe vertebral artery autophagosomes.Western blotting was used to detect the ratios of phosphorylated(phospho)-phosphoinositide 3-kinase(PI3K)/PI3K,phospho-Akt/Akt,phospho-mTOR/mTOR,autophagy-related proteins(Beclin-1 and p62),and the ratios of microtubule-associated protein 1A/1B light chain 3(LC3Ⅱ/LC3Ⅰ)in vertebral artery tissues.Results:Compared to the Sham group,the inclination angle of the inclined plate,pia mater microcirculation blood flow,blood flow velocity of the left vertebral artery(LVA),right vertebral artery(RVA),NO level,and SOD activity were significantly decreased(P<0.05),and the serum ET-1 and MDA levels were significantly increased(P<0.05)in the CSA group.Compared to the CSA group,the inclination angle of the inclined plate,blood flow of pia mater microcirculation,blood flow velocity of the LVA and RVA,NO level,and SOD activity were significantly increased(P<0.05),and the serum ET-1 and MDA levels were significantly decreased(P<0.05)in the fire needling group.The inclination angle of the inclined plate,blood flow of pia mater microcirculation,blood flow velocity of the LVA and RVA,NO level,and SOD activity in the fire needling+IGF-1 group were significantly lower than those in the fire needling group(P<0.05),and the serum ET-1 and MDA levels were higher than those in the fire needling group(P<0.05).Compared to the Sham group,a large number of autophagosomes and autophagy degradation vesicles were found in the vertebral artery tissues of the CSA group.Compared to the CSA group,autophagosomes and autophagy degradation vesicles in rat vertebral artery tissues of the fire needling group were significantly reduced.Compared to the fire needling group,the autophagosomes and autophagy degradation vesicles in the vertebral artery tissues of the fire needling+IGF-1 group were increased significantly.The expression ratios of phospho-PI3K/PI3K,phospho-Akt/Akt,phospho-mTOR/mTOR,LC3Ⅱ/LC3Ⅰ,and Beclin protein expression in rat vertebral artery tissues of the CSA group were higher than those in the Sham group(P<0.05),and p62 protein expression was lower than that in the Sham group(P<0.05).The above expression ratios in rat vertebral artery tissues of the fire needling group were lower than those of the CSA group(P<0.05),and p62 protein expression was higher than that of the CSA group(P<0.05).The above protein expression ratios in rat vertebral artery tissues of the fire needling+IGF-1 group were higher than those of the fire needling group(P<0.05),and p62 protein expression was lower than that of the fire needling group(P<0.05).Conclusion:Fire needling can reduce oxidative stress levels by promoting autophagy in CSA rats.The mechanism may be related to the inhibition of PI3K/Akt/mTOR signaling pathway activation.展开更多
Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is unknown whether the 5-hydroxytr...Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is unknown whether the 5-hydroxytryptamine 2A receptor（5-HT2AR） is involved in the effects of prenatal alcohol exposure. In the present study, pregnant female rats received drinking water containing alcohol at concentrations of 0%, 1%, 2%, 4%, 8% or 10%（v/v） throughout the gestation period. Slices of the medulla from 2-day-old neonatal rats were obtained to record respiratory rhythmical discharge activity. 5-HT2 AR protein and m RNA levels in the pre-B？tzinger complex of the respiratory center were measured by western blot analysis and quantitative RT-PCR, respectively. Compared with the 0% alcohol group, respiratory rhythmical discharge activity in medullary slices in the 4%, 8% and 10% alcohol groups was decreased, and the reduction was greatest in the 8% alcohol group. Respiratory rhythmical discharge activity in the 10% alcohol group was irregular. Thus, 8% was the most effective alcohol concentration at attenuating respiratory rhythmical discharge activity. These findings suggest that prenatal alcohol exposure attenuates respiratory rhythmical discharge activity in neonatal rats by downregulating 5-HT2 AR protein and m RNA levels.展开更多
Background:Adenoid hypertrophy(AH)is a common pediatric disease that signifi-cantly impacts the growth and quality of life of children.However,there is no replica-ble and valid model for AH.Methods:An AH rat model was...Background:Adenoid hypertrophy(AH)is a common pediatric disease that signifi-cantly impacts the growth and quality of life of children.However,there is no replica-ble and valid model for AH.Methods:An AH rat model was developed via comprehensive allergic sensitization,chronic inflammation induction,and chronic intermittent hypoxia(CIH).The modeling process involved three steps:female Sprague-Dawley rats(aged 4-5 weeks)were used for modeling.Allergen sensitization was induced via intraperitoneal administra-tion and intranasal provocation using ovalbumin(OVA);chronic nasal inflammation was induced through intranasal lipopolysaccharide(LPS)administration for sustained nasal irritation;CIH akin to obstructive sleep apnea/hypopnea syndrome was induced using an animal hypoxia chamber.Postmodel establishment,behaviors,and histologi-cal changes in nasopharynx-associated lymphoid tissue(NALT)and nasal mucosa were assessed.Arterial blood gas analysis and quantification of serum and tissue levels of(interleukin)IL-4 and IL-13,OVA-specific immunoglobulin E(sIgE),eosinophil cationic protein(ECP),tumor necrosis factor(TNF-α),IL-17,and transforming growth factor(TGF)-βwere conducted for assessment.The treatment group received a combination of mometasone furoate and montelukast sodium for a week and then was evaluated.Results:Rats exhibited notable nasal symptoms and hypoxia after modeling.Histopathological analysis revealed NALT follicle hypertrophy and nasal mucosa in-flammatory cell infiltration.Elevated IL-4,IL-13,IL-17,OVA-sIgE,ECP,and TNF-αlev-els and reduced TGF-βlevels were observed in the serum and tissue of model-group rats.After a week of treatment,the treatment group exhibited symptom and inflam-matory factor improvement.Conclusion:The model effectively simulates AH symptoms and pathological changes.But it should be further validated for genetic,immunological,and hormonal back-grounds in the currently used and other strains and species.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
This study aims to conduct a comparative study of two strains of laboratoryrats,hooded and Wistar,to select a suitable alternative to nude rats for ovariantissue xenotransplantation.The study investigated the effects ...This study aims to conduct a comparative study of two strains of laboratoryrats,hooded and Wistar,to select a suitable alternative to nude rats for ovariantissue xenotransplantation.The study investigated the effects of ovarian tissuetransplantation using three experimental groups:(1)the control group receivingvitrified-warmed human ovarian tissue,(2)the OTW(ovarian tissue transplantationin Wistar)group with human ovarian tissues in Wistar rats,and(3)the OTH(ovariantissue transplantation in hooded)group with ovarian tissues transplanted into hoodedrats.A total of 12 rats(6 each from the two transplantation groups)were used,withtissue samples implanted in the dorsal neck muscles.Outcomes were evaluatedusing histological analyses,including hematoxylin and eosin and Masson's trichromestaining,as well as immunohistochemical assessments of CD31 for angiogenesis,fibrosis,and necrosis.The OTH group exhibited more blood vessel numbers and theVegf gene expression than both the OTW and control groups,with significantly lowerlevels of fibrosis and necrosis compared to the OTW and control groups.The studyindicates that hooded rats could serve as a valuable alternative for specific researchwhen nude mice are not available.Their immune systems are more compatible withhuman ovarian tissue transplants than Wistar rats,and they exhibit calmer behaviors,making them better suited for laboratory work.展开更多
Background:Scientific animal models are indispensable for studying trauma repair.This work aimed at establishing a more scientific rat trauma model by studying different rat trauma models caused by different trauma nu...Background:Scientific animal models are indispensable for studying trauma repair.This work aimed at establishing a more scientific rat trauma model by studying different rat trauma models caused by different trauma numbers,locations,and trauma attachment tension unloaders and rat age.Methods:A four-trauma self-upper,lower,left and right control model;a two-trauma self-trauma bare and ring control model;and a young and old rat trauma model were created to evaluate the condition of these traumas.Results:In the four-trauma self-control model,the healing status of the upper proximal cephalic trauma was better than that of the lower proximal caudal trauma,whereas there was no significant difference between the left and right trauma.The healing rate and postwound condition of the trauma with a ring control in the two-trauma model were better than those of the bare side.The healing speed of the old rats was slower,and the amount of extracellular matrix in the subcutaneous tissue after healing was significantly lower than that of the young rats.Conclusion:The double trauma with a ring is a more scientific and reasonable experimental model.There is a significant difference between young and old rats in the wound healing process.Therefore,the appropriate age of the rats should be selected according to the main age range of the patients with similar conditions in the clinical setting being mimicked.展开更多
ZSF1 lean rats are widely used as controls in cardiometabolic studies involving ZSF1 obese rats,which develop a cardiometabolic syndrome and diastolic dysfunction at a young age due to a double leptin receptor mutatio...ZSF1 lean rats are widely used as controls in cardiometabolic studies involving ZSF1 obese rats,which develop a cardiometabolic syndrome and diastolic dysfunction at a young age due to a double leptin receptor mutation(Lepr^(cp)and Lepr^(fa)).Although,lean littermates show no overt signs of cardiometabolic disease or diastolic impact,they belong to one of three genotypic variants,two of which carry one of the mutant Lepr alleles and,thus,doubt has been raised about their suitability as healthy controls.We compared 32-week-old female ZSF1 lean and Wistar rats regarding physiological,myocardial,vascular,skeletal muscle,and mitochondrial characteristics.Lean rats showed lower body weight but increased heart,kidney,and skeletal muscle mass.Despite thicker ventricular walls,systolic and diastolic function were preserved.Hemodynamically measured contractility was higher as underpinned by a higher mitochondrial respiratory capacity of LV fibers.However,left ventricular filling pressure was elevated,accompanied by increased ventricular stiffness.Endothelial function was preserved,but smooth muscle responsiveness was reduced,indicated by impaired SNP-induced relaxation.Passive vascular stiffness mediated by collagenous fibers was significantly higher in lean rats.Skeletal muscle function was mostly preserved,though maximal specific force of the EDL was reduced.Taken together,ZSF1 lean rats are physiologically different from Wistar rats as they display enlarged myocardial dimensions accompanied by increased blood pressure and an incipient diastolic and vascular stiffness.Therefore,our data indicate an early phase of passive compliance disorder in ZSF1 lean animals,which might become more pronounced at an advanced age.展开更多
The COVID-19 pandemic posed a challenge for clinical management of a new lung disease that was characterized by inflammation,endothelial cell dysfunction,and thrombosis,which occur after the replication phase of infec...The COVID-19 pandemic posed a challenge for clinical management of a new lung disease that was characterized by inflammation,endothelial cell dysfunction,and thrombosis,which occur after the replication phase of infection of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).There are many laboratory models of active SARS-CoV-2 infection in mice,reflecting an acute lung injury in an otherwise healthy animal,but there is a lack of accurate animal models of the postviral inflammatory phase of the COVID-19 lung reflecting severe disease.The monocrotaline(MCT)-treated rat is a widely used laboratory model of pulmonary hypertension(PH).Not often discussed,however,are the observed changes in inflammation,edema,fibrosis,and microthrombosis in the lung prior to PH.At the cellular level,there is loss of pneumocytes and endotheliopathy,and at the molecular level the MCT rat lung is characterized by a proinflammatory cytokine profile,namely elevated interleukin 6,transforming growth factorβand tumor necrosis factor,M1 macrophage phenotype,and dysregulation of the angiotensin converting enzyme(ACE)/ACE2 balance.The systems-level pathophysiology of the MCT-treated rat includes progressive cardiopulmonary dysfunction.The MCT-treated rat clearly differs from the COVID-19 lung in terms of the triggers for pathology,but there are many parallels apparent in both the MCT-treated rat and the COVID-19 lung.The MCT-treated rat lung as a model of the COVID-19 lung may provide an in-depth understanding of the factors that drive the lung to more severe pathology,treatments that benefit lung recovery,or the factors that prove a useful research platform for future emerging respiratory threats of similar pathology.展开更多
Repetitive magnetic stimulation has been shown to alter local blood flow of the brain, excite the corticospinal tract and muscle, and induce motor function recovery. We established a rat model of acute spinal cord inj...Repetitive magnetic stimulation has been shown to alter local blood flow of the brain, excite the corticospinal tract and muscle, and induce motor function recovery. We established a rat model of acute spinal cord injury using the modified Allen＇s method. After 4 hours of injury, rat models received repetitive magnetic stimulation, with a stimulus intensity of 35% maximum output intensity, 5-Hz frequency, 5 seconds for each sequence, and an interval of 2 minutes. This was repeated for a total of 10 sequences, once a day, 5 days in a week, for 2 consecutive weeks. After repetitive magnetic stimulation, the number of apoptotic cells decreased, matrix metalloproteinase 9/2 gene and protein expression decreased, nestin expression increased, somatosensory and motor-evoked potentials recovered, and motor function recovered in the injured spinal cord. These findings confirm that repetitive magnetic stimulation of the spinal cord improved the microenvironment of neural regeneration, reduced neuronal apoptosis, and induced neuroprotective and repair effects on the injured spinal cord.展开更多
Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential ...Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats （7 days old） subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2＇-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2＇- deoxyuddine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.展开更多
Dexmedetomidine has significant neuroprotective effects. However, whether its protective effects can reduce neurotoxicity caused by isoflurane in fetal brain during the second trimester of pregnancy remains unclear. I...Dexmedetomidine has significant neuroprotective effects. However, whether its protective effects can reduce neurotoxicity caused by isoflurane in fetal brain during the second trimester of pregnancy remains unclear. In this study, timed-pregnancy rats at gestational day 14 spontaneously inhaled 1.5% isoflurane for 4 hours, and were intraperitoneally injected with dexmedetomidine at dosages of 5, 10, 20, and 20 μg/kg 15 minutes before inhalation and after inhalation for 2 hours. Our results demonstrate that 4 hours after inhaling isoflurane, 20 μg/kg dexmedetomidine visibly mitigated isoflurane-induced neuronal apoptosis, reversed downregulation of brain-derived neurotrophic factor expression, and lessened decreased spatial learning and memory ability in adulthood in the fetal rats. Altogether, these findings indicate that dexmedetomidine can reduce neurodegeneration induced by isoflurane in fetal rats during the second trimester of pregnancy. Further, brain-derived neurotrophic factor participates in this process.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
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 Project of Zhangjiajie City’s Industry-Academia-Research Collaborative Innovation‘Open Project Leader’,Zhangjiajie City’s Project of Taking on Challenging Tasks by Responding to Calls for Solutions(JB20230530)Basic Research Funds Project for Central Universities of China(2023XCZX001,2020kfyXJJS120)Academician and Expert Workstations in Yunnan Province(202205AF150090).
文摘Vine tea is documented in ancient Chinese books as having the function of promoting blood circulation.However,its effects and mechanisms remain unclear.The aim of this study was to comprehensively investigate the protective potential and mechanisms of vine tea in high-fat diet rat through a combination of in vivo and in vitro experiments.The efficacy of vine tea was evaluated using a high-fat diet rat model and an oxidized low-density lipoprotein-treated cell model,with physiological and biochemical indicators measured in rat serum and cell supernatants.Transcriptomics was utilized to investigate alterations mRNA expression following the administration of dihydromyricetin in cell model.Metabolomics and 16S rRNA sequencing was employed to examine changes in metabolites in the serum and changes in gut microbiota of high-fat diet rats after administering vine tea extract.Vine tea extract and dihydromyricetin can reduce elevated levels of lipids,including total cholesterol and triglycerides,following modeling.Transcriptomic data indicate that dihydromyricetin exerts its effects by regulating ferroptosis signaling pathways.Metabolomic analysis demonstrates that the administration of vine tea extract influences the vitamin K cycle and glutathione,thereby alleviating the progression of ferroptosis.Additionally,16S rRNA sequencing reveals that vine tea extract increases Lactobacillaceae in the gut microbiota,which subsequently affects the levels of lysophosphatidylcholine,a major phospholipid component of oxidized low-density lipoprotein in serum.Our results indicate that vine tea can regulate ferroptosis signaling pathways and increase Lactobacillaceae in the gut microbiota,thereby exhibiting cardiovascular protective effects in high-fat diet rats.
基金Leducq Trans-Atlantic Network of Excellence,Grant/Award Number:TNE-21CVD04Spanish Ministry of Science and Innovation,Grant/Award Number:PID2020-117765RB-I00 and PID2022-140616OB-I00+1 种基金Instituto de Salud Carlos III,European Development Regional Fund,RICORS-ICTUS Grant/Award Number:RD21/0006/0001the FORTALECE program.Grant/Award Number:FORT23/00023。
文摘Stroke induces profound neuroinflammation and systemic immune dysregulation,including disturbances in gut homeostasis.Experimental evidence suggests that intestinal barrier permeability(IBP)and bacterial translocation(BT)critically influence stroke outcomes.However,biological variability among commonly used rodent substrains has received limited attention.In this pilot study,we compared poststroke immune responses in two Wistar rat substrains obtained from different suppliers:RccHan(Envigo)and RjHan(Janvier).Naive animals(n=4)and rats subjected to permanent cerebral ischemia(n=8 per substrain)were evaluated 72 h after middle cerebral artery occlusion and stratified according to the presence or absence of BT.Immune cell populations in blood and bone marrow were analyzed using flow cytometry,and leukocyte infiltration into ischemic brain tissue was quantified using immunohisto-chemistry.Differences were considered statistically significant when p<0.05.Both substrains developed significant infarcts and neurological deficits.RccHan rats exhibited larger infarct volumes and more extensive BT across multiple organs.In contrast,RjHan rats exhibited BT mainly confined to mesenteric lymph nodes but exhibited greater IBP.Although dissemination was broader in RccHan rats,overall bacterial burden was slightly lower compared with RjHan,and extraintestinal bacterial composition differed between groups.Particularly,RjHan rats exhibited stronger systemic and central immune activation,with significant alterations in lymphocyte and monocyte populations and enhanced granulocyte and T-cell infiltration within ischemic lesions.These findings demonstrate that substrain origin profoundly influences poststroke intestinal barrier integrity,bacterial dissemination,and immune responses considering substrain-related variability is essential to improve reproducibility and translational relevance in preclinical stroke research.
文摘AIM:To investigate the effects of zingerone(ZO)on the retina in diabetic rats.METHODS:A total of 70 rats were randomly selected and divided into seven groups[diabetic group(Dm+;n=10),diabetic+metformin group(Dm+Met;n=10),diabetic+ZO25 group(Dm+ZO25;n=10),diabetic+ZO50 group(Dm+ZO50;n=10),diabetic+metformin group+ZO 50 Group(Dm+Met+ZO50;n=10)].Diabetes was induced by streptozotocin(STZ),and metformin and two different doses of ZO were administered via gavage.Retinal tissues were evaluated by histopathological and immunohistochemical analyses.RESULTS:In diabetic rats,severe retinal inflammation,tissue necrosis,and increased tumor necrosis factor-α(TNF-α)expression were observed.ZO administration reduced these effects in a dose-dependent manner.Protective effects of metformin alone were limited,and no synergistic benefit was observed in ZO+Met groups.Administration of 50 mg/kg ZO to non-diabetic rats caused no retinal toxicity.Additionally,elevated 8-OHdG and c-Jun N-terminal kinase(JNK)expressions in diabetic retinopathy models were significantly reduced by ZO treatment.CONCLUSION:ZO can markedly reduce the pathological effects of the retina in a diabetic rat model.
文摘AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided into four equal groups(n=6/group)as follows:healthy group(HG),ATP-only group(ATPG),sildenafil-onlygroup(SILG),and ATP+sildenafil group(ATP+SLD).ATPG andATP+SLD groups were injected intraperitoneally with ATP(4 mg/kg),while SILG and HG groups were injected withsaline(0.9%NaCl)by the same route as a solvent.One hourafter the administration of ATP and solvent,sildenafil(10 m g/k g)was administered orally to the SILG andATP+SLD groups.This procedure was repeated once a dayfor 4wk.The animals were then sacrificed,eyeballs wereremoved and oxidant and antioxidant parameters weremeasured biochemically.Additionally,the ocular tissueswere evaluated histopathologically.RESULTS:Sildenafil increased oxidant(malondialdehyde)levels and decreased antioxidant levels(total glutathione,superoxide dismutase,catalase)in rat ocular tissues andcaused severe oxidative stress.In addition,sildenafil hasbeen shown histopathologically to cause oxidative damagein retinal layers.ATP treatment suppressed oxidative stressand attenuated histopathological damage in the retinal layers.CONCLUSION:ATP protects retinal tissue againstsildenafil-induced ocular oxidative damage in rats andmay contribute to the development of novel approaches toprevent or treat this damage.
基金Outstanding Young Investigator Program of Capital Medical University,Grant/Award Number:A2308。
文摘Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established an omohyoid muscle-based PNS rat model combined with MV.Bilateral nerves were exposed within 20±2 min by transection at the intermediate tendon of omohyoid muscle,minimizing trauma and bleeding.Threshold stimulation(0.6±0.2 mA)correlated with body weight.Ventilator-synchronized stimulation increased compound muscle action potentials by~30%,whereas histology confirmed intact nerve.Physiological parameters remained stable throughout ventilation.This model provides a safe and scalable platform for mechanistic and preclinical studies on PNS-mediated protection against MV-induced organ injury.
基金supported by Chongqing Science and Technology Project of Traditional Chinese Medicine Jointly Launched by Science and Health Commission in 2018(重庆市2018年科卫联合中医药科技项目,No.ZY201802027).
文摘Objective:To investigate the mechanism of fire needling in improving autophagy and oxidative stress in rats with cervical spondylosis of vertebral artery type(CSA)by regulating protein kinase B(PKB/Akt)/mammalian target of rapamycin(mTOR)signaling pathway.Methods:The rats were randomly divided into a sham-operation group(Sham group)and a model group.After successful modeling,the rats were randomly divided into a CSA group,a fire needling group,and a fire needling+insulin-like growth factor 1(IGF-1)group.No intervention was performed in the Sham and CSA groups;the fire needling group received fire needling intervention;the fire needling+IGF-1 group received both fire needling and intraperitoneal injection of IGF-1 solution intervention.The inclined plate test was used to detect the exercise ability of rats.Laser Doppler was used to detect the blood flow in the pia mater microcirculation.Multi-mode high-frequency acoustic was used to detect the blood flow velocity of both sides of the vertebral artery.The serum levels of endothelin-1(ET-1),nitric oxide(NO),superoxide dismutase(SOD),and malondialdehyde(MDA)were measured.A transmission electron microscope was used to observe vertebral artery autophagosomes.Western blotting was used to detect the ratios of phosphorylated(phospho)-phosphoinositide 3-kinase(PI3K)/PI3K,phospho-Akt/Akt,phospho-mTOR/mTOR,autophagy-related proteins(Beclin-1 and p62),and the ratios of microtubule-associated protein 1A/1B light chain 3(LC3Ⅱ/LC3Ⅰ)in vertebral artery tissues.Results:Compared to the Sham group,the inclination angle of the inclined plate,pia mater microcirculation blood flow,blood flow velocity of the left vertebral artery(LVA),right vertebral artery(RVA),NO level,and SOD activity were significantly decreased(P<0.05),and the serum ET-1 and MDA levels were significantly increased(P<0.05)in the CSA group.Compared to the CSA group,the inclination angle of the inclined plate,blood flow of pia mater microcirculation,blood flow velocity of the LVA and RVA,NO level,and SOD activity were significantly increased(P<0.05),and the serum ET-1 and MDA levels were significantly decreased(P<0.05)in the fire needling group.The inclination angle of the inclined plate,blood flow of pia mater microcirculation,blood flow velocity of the LVA and RVA,NO level,and SOD activity in the fire needling+IGF-1 group were significantly lower than those in the fire needling group(P<0.05),and the serum ET-1 and MDA levels were higher than those in the fire needling group(P<0.05).Compared to the Sham group,a large number of autophagosomes and autophagy degradation vesicles were found in the vertebral artery tissues of the CSA group.Compared to the CSA group,autophagosomes and autophagy degradation vesicles in rat vertebral artery tissues of the fire needling group were significantly reduced.Compared to the fire needling group,the autophagosomes and autophagy degradation vesicles in the vertebral artery tissues of the fire needling+IGF-1 group were increased significantly.The expression ratios of phospho-PI3K/PI3K,phospho-Akt/Akt,phospho-mTOR/mTOR,LC3Ⅱ/LC3Ⅰ,and Beclin protein expression in rat vertebral artery tissues of the CSA group were higher than those in the Sham group(P<0.05),and p62 protein expression was lower than that in the Sham group(P<0.05).The above expression ratios in rat vertebral artery tissues of the fire needling group were lower than those of the CSA group(P<0.05),and p62 protein expression was higher than that of the CSA group(P<0.05).The above protein expression ratios in rat vertebral artery tissues of the fire needling+IGF-1 group were higher than those of the fire needling group(P<0.05),and p62 protein expression was lower than that of the fire needling group(P<0.05).Conclusion:Fire needling can reduce oxidative stress levels by promoting autophagy in CSA rats.The mechanism may be related to the inhibition of PI3K/Akt/mTOR signaling pathway activation.
基金the Natural Science Foundation of Henan Province in China,No.102102310156the Foundation of Xinxiang Technology Bureau in China,No.ZG14004
文摘Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is unknown whether the 5-hydroxytryptamine 2A receptor（5-HT2AR） is involved in the effects of prenatal alcohol exposure. In the present study, pregnant female rats received drinking water containing alcohol at concentrations of 0%, 1%, 2%, 4%, 8% or 10%（v/v） throughout the gestation period. Slices of the medulla from 2-day-old neonatal rats were obtained to record respiratory rhythmical discharge activity. 5-HT2 AR protein and m RNA levels in the pre-B？tzinger complex of the respiratory center were measured by western blot analysis and quantitative RT-PCR, respectively. Compared with the 0% alcohol group, respiratory rhythmical discharge activity in medullary slices in the 4%, 8% and 10% alcohol groups was decreased, and the reduction was greatest in the 8% alcohol group. Respiratory rhythmical discharge activity in the 10% alcohol group was irregular. Thus, 8% was the most effective alcohol concentration at attenuating respiratory rhythmical discharge activity. These findings suggest that prenatal alcohol exposure attenuates respiratory rhythmical discharge activity in neonatal rats by downregulating 5-HT2 AR protein and m RNA levels.
基金This work was financially supported by the National Natural Science Foundation of China(grant number:8217150152)the Clinical Science and Technology Innovation Project of Shanghai Shenkang Hospital Development Center(grant number:SHDC12021102)the Shanghai Three-Year Action Plan to Further Accelerate the Development of Traditional Chinese Medicine Inheritance and Innovation(grant number:ZY(2021-2023)-0209-05).
文摘Background:Adenoid hypertrophy(AH)is a common pediatric disease that signifi-cantly impacts the growth and quality of life of children.However,there is no replica-ble and valid model for AH.Methods:An AH rat model was developed via comprehensive allergic sensitization,chronic inflammation induction,and chronic intermittent hypoxia(CIH).The modeling process involved three steps:female Sprague-Dawley rats(aged 4-5 weeks)were used for modeling.Allergen sensitization was induced via intraperitoneal administra-tion and intranasal provocation using ovalbumin(OVA);chronic nasal inflammation was induced through intranasal lipopolysaccharide(LPS)administration for sustained nasal irritation;CIH akin to obstructive sleep apnea/hypopnea syndrome was induced using an animal hypoxia chamber.Postmodel establishment,behaviors,and histologi-cal changes in nasopharynx-associated lymphoid tissue(NALT)and nasal mucosa were assessed.Arterial blood gas analysis and quantification of serum and tissue levels of(interleukin)IL-4 and IL-13,OVA-specific immunoglobulin E(sIgE),eosinophil cationic protein(ECP),tumor necrosis factor(TNF-α),IL-17,and transforming growth factor(TGF)-βwere conducted for assessment.The treatment group received a combination of mometasone furoate and montelukast sodium for a week and then was evaluated.Results:Rats exhibited notable nasal symptoms and hypoxia after modeling.Histopathological analysis revealed NALT follicle hypertrophy and nasal mucosa in-flammatory cell infiltration.Elevated IL-4,IL-13,IL-17,OVA-sIgE,ECP,and TNF-αlev-els and reduced TGF-βlevels were observed in the serum and tissue of model-group rats.After a week of treatment,the treatment group exhibited symptom and inflam-matory factor improvement.Conclusion:The model effectively simulates AH symptoms and pathological changes.But it should be further validated for genetic,immunological,and hormonal back-grounds in the currently used and other strains and species.
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This study aims to conduct a comparative study of two strains of laboratoryrats,hooded and Wistar,to select a suitable alternative to nude rats for ovariantissue xenotransplantation.The study investigated the effects of ovarian tissuetransplantation using three experimental groups:(1)the control group receivingvitrified-warmed human ovarian tissue,(2)the OTW(ovarian tissue transplantationin Wistar)group with human ovarian tissues in Wistar rats,and(3)the OTH(ovariantissue transplantation in hooded)group with ovarian tissues transplanted into hoodedrats.A total of 12 rats(6 each from the two transplantation groups)were used,withtissue samples implanted in the dorsal neck muscles.Outcomes were evaluatedusing histological analyses,including hematoxylin and eosin and Masson's trichromestaining,as well as immunohistochemical assessments of CD31 for angiogenesis,fibrosis,and necrosis.The OTH group exhibited more blood vessel numbers and theVegf gene expression than both the OTW and control groups,with significantly lowerlevels of fibrosis and necrosis compared to the OTW and control groups.The studyindicates that hooded rats could serve as a valuable alternative for specific researchwhen nude mice are not available.Their immune systems are more compatible withhuman ovarian tissue transplants than Wistar rats,and they exhibit calmer behaviors,making them better suited for laboratory work.
基金Shandong Provincial Natural Science Foundation,Grant/Award Number:ZR2022MH211the Key Program of Shandong Provincial Natural Science Foundation,Grant/Award Number:ZR2020KE018National Natural Science Foundation of China,Grant/Award Number:52003068。
文摘Background:Scientific animal models are indispensable for studying trauma repair.This work aimed at establishing a more scientific rat trauma model by studying different rat trauma models caused by different trauma numbers,locations,and trauma attachment tension unloaders and rat age.Methods:A four-trauma self-upper,lower,left and right control model;a two-trauma self-trauma bare and ring control model;and a young and old rat trauma model were created to evaluate the condition of these traumas.Results:In the four-trauma self-control model,the healing status of the upper proximal cephalic trauma was better than that of the lower proximal caudal trauma,whereas there was no significant difference between the left and right trauma.The healing rate and postwound condition of the trauma with a ring control in the two-trauma model were better than those of the bare side.The healing speed of the old rats was slower,and the amount of extracellular matrix in the subcutaneous tissue after healing was significantly lower than that of the young rats.Conclusion:The double trauma with a ring is a more scientific and reasonable experimental model.There is a significant difference between young and old rats in the wound healing process.Therefore,the appropriate age of the rats should be selected according to the main age range of the patients with similar conditions in the clinical setting being mimicked.
文摘ZSF1 lean rats are widely used as controls in cardiometabolic studies involving ZSF1 obese rats,which develop a cardiometabolic syndrome and diastolic dysfunction at a young age due to a double leptin receptor mutation(Lepr^(cp)and Lepr^(fa)).Although,lean littermates show no overt signs of cardiometabolic disease or diastolic impact,they belong to one of three genotypic variants,two of which carry one of the mutant Lepr alleles and,thus,doubt has been raised about their suitability as healthy controls.We compared 32-week-old female ZSF1 lean and Wistar rats regarding physiological,myocardial,vascular,skeletal muscle,and mitochondrial characteristics.Lean rats showed lower body weight but increased heart,kidney,and skeletal muscle mass.Despite thicker ventricular walls,systolic and diastolic function were preserved.Hemodynamically measured contractility was higher as underpinned by a higher mitochondrial respiratory capacity of LV fibers.However,left ventricular filling pressure was elevated,accompanied by increased ventricular stiffness.Endothelial function was preserved,but smooth muscle responsiveness was reduced,indicated by impaired SNP-induced relaxation.Passive vascular stiffness mediated by collagenous fibers was significantly higher in lean rats.Skeletal muscle function was mostly preserved,though maximal specific force of the EDL was reduced.Taken together,ZSF1 lean rats are physiologically different from Wistar rats as they display enlarged myocardial dimensions accompanied by increased blood pressure and an incipient diastolic and vascular stiffness.Therefore,our data indicate an early phase of passive compliance disorder in ZSF1 lean animals,which might become more pronounced at an advanced age.
基金College of Medicine and Public Health,MD,Advanced Studies ProgramAustralian National Health and Medical Research Council(NHMRC),Grant/Award Number:GNT2003683。
文摘The COVID-19 pandemic posed a challenge for clinical management of a new lung disease that was characterized by inflammation,endothelial cell dysfunction,and thrombosis,which occur after the replication phase of infection of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).There are many laboratory models of active SARS-CoV-2 infection in mice,reflecting an acute lung injury in an otherwise healthy animal,but there is a lack of accurate animal models of the postviral inflammatory phase of the COVID-19 lung reflecting severe disease.The monocrotaline(MCT)-treated rat is a widely used laboratory model of pulmonary hypertension(PH).Not often discussed,however,are the observed changes in inflammation,edema,fibrosis,and microthrombosis in the lung prior to PH.At the cellular level,there is loss of pneumocytes and endotheliopathy,and at the molecular level the MCT rat lung is characterized by a proinflammatory cytokine profile,namely elevated interleukin 6,transforming growth factorβand tumor necrosis factor,M1 macrophage phenotype,and dysregulation of the angiotensin converting enzyme(ACE)/ACE2 balance.The systems-level pathophysiology of the MCT-treated rat includes progressive cardiopulmonary dysfunction.The MCT-treated rat clearly differs from the COVID-19 lung in terms of the triggers for pathology,but there are many parallels apparent in both the MCT-treated rat and the COVID-19 lung.The MCT-treated rat lung as a model of the COVID-19 lung may provide an in-depth understanding of the factors that drive the lung to more severe pathology,treatments that benefit lung recovery,or the factors that prove a useful research platform for future emerging respiratory threats of similar pathology.
文摘Repetitive magnetic stimulation has been shown to alter local blood flow of the brain, excite the corticospinal tract and muscle, and induce motor function recovery. We established a rat model of acute spinal cord injury using the modified Allen＇s method. After 4 hours of injury, rat models received repetitive magnetic stimulation, with a stimulus intensity of 35% maximum output intensity, 5-Hz frequency, 5 seconds for each sequence, and an interval of 2 minutes. This was repeated for a total of 10 sequences, once a day, 5 days in a week, for 2 consecutive weeks. After repetitive magnetic stimulation, the number of apoptotic cells decreased, matrix metalloproteinase 9/2 gene and protein expression decreased, nestin expression increased, somatosensory and motor-evoked potentials recovered, and motor function recovered in the injured spinal cord. These findings confirm that repetitive magnetic stimulation of the spinal cord improved the microenvironment of neural regeneration, reduced neuronal apoptosis, and induced neuroprotective and repair effects on the injured spinal cord.
基金supported by Guangdong Province Science Research Project,No.B30502
文摘Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats （7 days old） subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2＇-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2＇- deoxyuddine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.
基金supported by the Medical Scientific Research Foundation of Guangdong Province of China,No.A2015619
文摘Dexmedetomidine has significant neuroprotective effects. However, whether its protective effects can reduce neurotoxicity caused by isoflurane in fetal brain during the second trimester of pregnancy remains unclear. In this study, timed-pregnancy rats at gestational day 14 spontaneously inhaled 1.5% isoflurane for 4 hours, and were intraperitoneally injected with dexmedetomidine at dosages of 5, 10, 20, and 20 μg/kg 15 minutes before inhalation and after inhalation for 2 hours. Our results demonstrate that 4 hours after inhaling isoflurane, 20 μg/kg dexmedetomidine visibly mitigated isoflurane-induced neuronal apoptosis, reversed downregulation of brain-derived neurotrophic factor expression, and lessened decreased spatial learning and memory ability in adulthood in the fetal rats. Altogether, these findings indicate that dexmedetomidine can reduce neurodegeneration induced by isoflurane in fetal rats during the second trimester of pregnancy. Further, brain-derived neurotrophic factor participates in this process.
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.
