This review focuses on rat models for studying the short-term and long-term effects of mild and severe hypoglycemia.We explored the physiological mechanisms to understand the consequences of hypoglycemia in rat experi...This review focuses on rat models for studying the short-term and long-term effects of mild and severe hypoglycemia.We explored the physiological mechanisms to understand the consequences of hypoglycemia in rat experimental models.This study aims to investigate the therapeutic potential of phytotherapeutic agents and their efficacy in mitigating the adverse effects of hypoglycemia.Insights from our planned research will be beneficial in improving quality of life for individuals at risk of episodes of low blood sugar.Optimizing hypoglycemic rat models for research requires selecting a suitable experimental model that will be susceptible to hypoglycemia induction,effective monitoring of blood glucose levels,and maintaining a high survival rate throughout the required experimental duration.展开更多
Frozen shoulder(FS),also known as adhesive capsulitis,is a condition that causes contraction and stiffness of the shoulder joint capsule.The main symptoms are per-sistent shoulder pain and a limited range of motion in...Frozen shoulder(FS),also known as adhesive capsulitis,is a condition that causes contraction and stiffness of the shoulder joint capsule.The main symptoms are per-sistent shoulder pain and a limited range of motion in all directions.These symp-toms and poor prognosis affect people's physical health and quality of life.Currently,the specific mechanisms of FS remain unclear,and there is variability in treatment methods and their efficacy.Additionally,the early symptoms of FS are difficult to distinguish from those of other shoulder diseases,complicating early diagnosis and treatment.Therefore,it is necessary to develop and utilize animal models to under-stand the pathogenesis of FS and to explore treatment strategies,providing insights into the prevention and treatment of human FS.This paper reviews the rat models available for FS research,including external immobilization models,surgical internal immobilization models,injection modeling models,and endocrine modeling models.It introduces the basic procedures for these models and compares and analyzes the advantages,disadvantages,and applicability of each modeling method.Finally,our paper summarizes the common methods for evaluating FS rat models.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
Chronic pain after spine surgery(CPSS)is a complex disorder characterized by multifactorial pathogenesis that occurs in 8%–40%of patients undergoing lumbar spine surgery.We aimed to develop a rat model that mimics cl...Chronic pain after spine surgery(CPSS)is a complex disorder characterized by multifactorial pathogenesis that occurs in 8%–40%of patients undergoing lumbar spine surgery.We aimed to develop a rat model that mimics clinical CPSS conditions by taking two sequential surgical procedures.Step 1:A plastic rod was inserted into the left L5 intervertebral foramen to produce a steady compression on the dorsal root ganglion(DRG)and the spinal nerve,a common cause of low back pain(LBP).Step 2:The rod was removed after 7 days when rats exhibited mechanical and heat hypersensitivity in the ipsilateral hindpaw,followed by a full L5 laminectomy to mimic spine decompression surgery in LBP patients.The retention of the rod induced a prolonged LBP-like behavior but was quickly resolved after rod removal without laminectomy.However,rats that received laminectomy after rod removal developed heightened mechanical and heat sensitivity in the hindpaw,impaired gait,and reduced spontaneous exploration activity,indicating CPSS.Patch clamp recording revealed a significant augmentation in the intrinsic excitability of smalldiameter DRG neurons in CPSS rats.Administration of Dermorphin[D-Arg2,Lys4](1–4)amide(DALDA,5mg/kg,i.p.),a peripherally acting mu-opioid receptor(MOR)-preferred agonist,attenuated pain hypersensitivity,capsaicin-induced[Ca^(2+)]i rising and the increased intrinsic excitability of DRG neurons from CPSS rats.Our findings suggest that this new model,which mirrors the nature of CPSS developed in patients,may be useful for future studies of the underlying mechanisms.展开更多
AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential stress.METHODS Animal pups were divided into two groups from postnatal day 2: control...AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential stress.METHODS Animal pups were divided into two groups from postnatal day 2: controls and the sequential-stress-treated. The sequential-stress-treated group received maternal separation and acute gastric irritation early in life and restraint stress in adulthood; controls were reared undisturbed with their mothers. Rats in both groups were followed to adulthood(8 wk) at which point the anxietylike behaviors and visceromotor responses to gastric distention(20-100 mm Hg) and gastric emptying were tested. Meanwhile, alterations in several anxiety-related brain-stomach modulators including 5-hydroxytryptamine(5-HT), γ-aminobutyric acid(GABA), brain-derived neurotrophic factor(BDNF) and nesfatin-1 in the rat hippocampus, plasma and gastric fundus and the 5-HT1 A receptor(5-HT1 AR) in the hippocampal CA1 subfield and the mucosa of the gastric fundus were examined.RESULTS Sequential-stress-treated rats simultaneously demonstrated anxiety-like behaviors and GHS in dose-dependent manner compared with the control group. Although rats in both groups consumed similar amount of solid food, the rate of gastric emptying was lower in the sequentialstress-treated rats than in the control group. Sequential stress significantly decreased the levels of 5-HT(51.91 ± 1.88 vs 104.21 ± 2.88, P < 0.01), GABA(2.38 ± 0.16 vs 5.01 ± 0.13, P < 0.01) and BDNF(304.40 ± 10.16 vs 698.17 ± 27.91, P < 0.01) in the hippocampus but increased the content of nesfatin-1(1961.38 ± 56.89 vs 1007.50 ± 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT(47.82 ± 2.29 vs 89.45 ± 2.61, P < 0.01) and BDNF(257.05 ± 12.89 vs 536.71 ± 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it(1391.75 ± 42.77 vs 737.88 ± 33.15, P < 0.01); significantly decreased the levels of 5-HT(41.15 ± 1.81 vs 89.17 ± 2.31, P < 0.01) and BDNF(226.49 ± 12.10 vs 551.36 ± 16.47, P < 0.01) in the gastric fundus but increased the content of nesfatin-1 in the same site(1534.75 ± 38.52 vs 819.63 ± 38.04, P < 0.01). The expressions of 5-HT1 AR in the hippocampal CA1 subfield and the mucosa of the gastric fundus were down-regulated measured by IHC(Optical Density value: Hippocampus 15253.50 ± 760.35 vs 21149.75 ± 834.13; gastric fundus 15865.25 ± 521.24 vs 23865.75 ± 1868.60; P < 0.05, respectively) and WB(0.38 ± 0.01 vs 0.57 ± 0.03, P < 0.01)(n = 8 in each group). CONCLUSION Sequential stress could induce a potential rat model of anxiety-like GHS of FD, which could be used to research the mechanisms of this intractable disease.展开更多
AIM:To develop a reliable,reproducible rat model of retinal vein occlusion(RVO)with a novel photosensitizer(erythrosin B)and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in a...AIM:To develop a reliable,reproducible rat model of retinal vein occlusion(RVO)with a novel photosensitizer(erythrosin B)and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in adult male rats via photochemically-induced ischemia.Retinal changes were monitored via color fundus photography and fluorescein angiography at 1 and 3h,and 1,4,7,14,and 21d after irradiation.Tissue slices were evaluated histopathologically.Retinal ganglion cell survival at different times after RVO induction was quantified by nuclear density count.Retinal thickness was also observed.RESULTS:For all rats in both the central and branch RVO groups,blood flow ceased immediately after laser irradiation and retinal edema was evident at one hour.The retinal detachment rate was 100%at 3h and developed into bullous retinal detachment within 24h.Retinal hemorrhages were not observed until 24h.Clearance of the occluded veins at 7d was observed by fluorescein angiography.Disease manifestation in the central RVO eyes was more severe than in the branch RVO group.A remarkable reduction in the ganglion cell count and retinal thickness was observed in the central RVO group by 21d,whereas moderate changes occurred in the branch RVO group.CONCLUSION:Rat RVO created by photochemicallyinduced ischemia using erythrosin B is a reproducible and reliable animal model for mimicking the key features of human RVO.However,considering the 100%rate ofretinal detachment,this animal model is more suitable for studying RVO with chronic retinal detachment.展开更多
AIM:To establish a rat model suitable to investigate the repetitive relapsing inflammations(RRI)characteristic to Crohn’s disease.METHODS:Colitis was induced by 2,4,6-trinitrobenzenesulfonic acid(TNBS).RRI were mimic...AIM:To establish a rat model suitable to investigate the repetitive relapsing inflammations(RRI)characteristic to Crohn’s disease.METHODS:Colitis was induced by 2,4,6-trinitrobenzenesulfonic acid(TNBS).RRI were mimicked by repeating administrations of TNBS.Tissue samples were taken from control,once,twice and three times treated rats from the inflamed and adjacent non-inflamed colonic segments at different timepoints during the acute intestinal inflammation.The means of the ulcerated area were measured to evaluate the macroscopic mu-cosal damage.The density of myenteric neurons was determined on whole mounts by Hu C/Hu D immunohistochemistry.Heme oxygenase-1(HO-1)expression was evaluated by molecular biological techniques.RESULTS:TNBS-treated rats displayed severe colitis,but the mortality was negligible,and an increase of body weight was characteristic throughout the experimental period.The widespread loss of myenteric neurons,and marked but transient HO-1 up-regulation were demonstrated after the first TNBS administration.After repeated doses the length of the recovery time and extent of the ulcerous colonic segments were markedly decreased,and the neuronal loss was on a smaller scale and was limited to the inflamed area.HO-1 m RNA level was notably greater than after a single dose and overexpression was sustained throughout the timepoints examined.Nevertheless,the HO-1protein up-regulation after the second TNBS treatment proved to be transient.Following the third treatment HO-1 protein expression could not be detected.CONCLUSION:Experimentally provoked RRI may exert a protective preconditioning effect against the mucosal and neuronal damage.The persistent up-regulation of HO-1 m RNA expression may correlate with this.展开更多
Objective:Herbal medicine is an important therapeutic option for benign prostatic hyperplasia(BPH),a common disease in older men that can seriously affect their quality of life.Currently,it is crucial to develop agent...Objective:Herbal medicine is an important therapeutic option for benign prostatic hyperplasia(BPH),a common disease in older men that can seriously affect their quality of life.Currently,it is crucial to develop agents with strong efficacy and few side effects.Herein we investigated the effects of the extract of Rauwolfia vomitoria,a shrub grown in West Africa,on BPH.Methods:Rats with testosterone-induced BPH were treated with R.vomitoria.Prostates were histologically analyzed by Hematoxylin and eosin staining.Proliferation index and the expression levels of androgen receptor and its associated proteins were quantified through immunohistochemistry and immunoblotting.Androgen receptor target genes were examined by quantitative real-time polymerase chain reaction.The sperm count and body weight of rats were also measured.Results:The oral administration of R.vomitoria extract significantly reduced the prostate weight and prostate weight index in BPH rats,supported by the decreased thickness of the prostate epithelial layer and increased lumen size.Similar effects were observed in the BPH rats treated with the reference drug,finasteride.R.vomitoria extract significantly reduced the testosterone-induced proliferation markers,including proliferating cell nuclear antigen and cyclin D1,in the prostate glands of BPH rats;it also reduced levels of androgen receptor,its associated protein steroid 5 a-reductase 1 and its downstream target genes(FK506-binding protein 5 and matrix metalloproteinase 2).Notably,compared with the finasteride group,R.vomitoria extract did not significantly reduce sperm count.Conclusion:R.vomitoria suppresses testosterone-induced BPH development.Due to its milder side effects,R.vomitoria could be a promising therapeutic agent for BPH.展开更多
AIM To establish a rat model of anal sphincter injury and test different systems to provide stem cells to injured area.METHODS Adipose-derived stem cells(ASCs)were isolated from BDIX rats and were transfected with gre...AIM To establish a rat model of anal sphincter injury and test different systems to provide stem cells to injured area.METHODS Adipose-derived stem cells(ASCs)were isolated from BDIX rats and were transfected with green fluorescent protein(GFP)for cell tracking.Biosutures(sutures covered with ASCs)were prepared with 1.5×10~6 GFPASCs,and solutions of 10~6 GFP-ASCs in normal saline were prepared for injection.Anorectal normal anatomy was studied on Wistar and BDIX female rats.Then,we designed an anal sphincter injury model consisting of a 1-cm extra-mucosal miotomy beginning at the anal verge in the anterior middle line.The sphincter lesion was confirmed with conventional histology(hematoxylin and eosin)and immunofluorescence with 4',6-diamidino-2-phenylindole(commonly known as DAPI),GFP andα-actin.Functional effect was assessed with basal anal manometry,prior to and after injury.After sphincter damage,36 BDIX rats were randomized to three groups for:(1)Cell injection without repair;(2)biosuture repair;and(3)conventional suture repair and cell injection.Functional and safety studies were conducted on all the animals.Rats were sacrificed after 1,4 or 7 d.Then,histological and immunofluorescence studies were performed on the surgical area.RESULTS With the described protocol,biosutures had been covered with at least 820000-860000 ASCs,with 100%viability.Our studies demonstrated that some ASCs remained adhered after suture passage through the muscle.Morphological assessment showed that the rat anal anatomy is comparable with human anatomy;two sphincters are present,but the external sphincter is poorly developed.Anal sphincter pressure data showed spontaneous,consistent,rhythmic anal contractions,taking the form of"plateaus"with multiple twitches(peaks)in each pressure wave.These basal contractions were very heterogeneous;their frequency was 0.91-4.17 per min(mean 1.6980,SD 0.57698),their mean duration was 26.67 s and mean number of peaks was 12.53.Our morphological assessment revealed that with the aforementioned surgical procedure,both sphincters were completely sectioned.In manometry,the described activity disappeared and was replaced by a gentle oscillation of basal line,without a recognizable pattern.Surprisingly,these findings appeared irrespective of injury repair or not.ASCs survived in this potentially septic area for 7 d,at least.We were able to identify them in 84%of animals,mainly in the muscular section area or in the tissue between the muscular endings.ASCs formed a kind of"conglomerate"in rats treated with injections,while in the biosuture group,they wrapped the suture.ASCs were also able to migrate to the damaged zone.No relevant adverse events or mortality could be related to the stem cells in our study.We also did not find unexpected tissue growths.CONCLUSION The proposed procedure produces a consistent sphincter lesion.Biosutures and injections are suitable for cell delivery.ASCs survive and are completely safe in this clinical setting.展开更多
AIM To develop a novel rat model of heterogeneous hepatic injury.METHODS Seventy male Sprague-Dawley rats were randomly divided into a control group(n = 10) and a colchicine group(n =60). A 0.25% colchicine solution(0...AIM To develop a novel rat model of heterogeneous hepatic injury.METHODS Seventy male Sprague-Dawley rats were randomly divided into a control group(n = 10) and a colchicine group(n =60). A 0.25% colchicine solution(0.4 mL/kg) was injected via the splenic vein in the colchicine group to develop a rat model of heterogeneous hepatic injury. An equal volume of normal saline was injected via the splenic vein in the control group. At days 3, 7, and 14 and weeks 4, 8, and 12 after the operation, at least seven rats of the colchicine group were selected randomly for magnetic resonance imaging(MRI) examinations, and then they were euthanized. Ten rats of the control group underwent MRI examinations at the same time points, and then were euthanized at week 12. T2-weighted images(T2 WI) and diffusion weighted imaging(DWI) were used to evaluate the heterogeneous hepatic injury. The heterogeneous injury between the left and right hepatic lobes was assessed on liver sections according to the histological scoring criteria, and correlated with the results of MRI study. RESULTS Obvious pathological changes occurred in the hepatic parenchyma in the colchicine group. Hepatic injury scores were significantly different between the left and right lobes at each time point(P < 0.05). There was a significant difference in apparent diffusion coefficient(ADC) of DWI and liver-to-muscle ratio(LMR) of T2 WI between the left and right lobes of rats in the colchicine group(P < 0.05) at each time point, and similar results were observed between the colchicine and control groups. Besides, there was a significant correlation between hepatic injury scores and ADC values or LMR(r =-0.682, P = 0.000; r =-0.245, P = 0.018).CONCLUSION Injection with colchicine via the splenic vein can be used to successfully develop a rat model of heterogeneous hepatic injury. DWI and T2 WI may help evaluate the heterogeneous injury among liver lobes.展开更多
Chronic alcoholism seriously damages the central nervous system and leads to impaired learning and memory.Cell damage in chronic alcoholism is strongly associated with elevated levels of hydrogen sulfide（H2S） and ca...Chronic alcoholism seriously damages the central nervous system and leads to impaired learning and memory.Cell damage in chronic alcoholism is strongly associated with elevated levels of hydrogen sulfide（H2S） and calcium ion overload.Aminooxyacetic acid is a cystathionine-β-synthase activity inhibitor that can reduce H2S formation in the brain.This study sought to observe the effect of aminooxyacetic acid on learning and memory in a chronic alcoholism rat model.Rats were randomly divided into three groups.Rats in the control group were given pure water for 28 days.Rats in the model group were given 6% alcohol for 28 days to establish an alcoholism rat model.Rats in the aminooxyacetic acid remedy group were also given 6% alcohol for 28 days and were also intraperitoneally injected daily with aminooxyacetic acid（5 mg/kg） from day 15 to day 28.Learning and memory was tested using the Morris water maze test.The ultrastructure of mitochondria in the hippocampus was observed by electron microscopy.H2S levels in the hippocampus were measured indirectly by spectrophotometry,and ATPase activity was measured using a commercial kit.The expression of myelin basic protein was determined by immunohistochemistry and western blotting.Compared with the control group,latency and swimming distance were prolonged in the navigation test on days 2,3,and 4 in the model group.In the spatial probe test on day 5,the number of platform crosses was reduced in the model group.Cristae cracks,swelling or deformation of mitochondria appeared in the hippocampus,the hippocampal H2S level was increased,the mitochondrial ATPase activity was decreased,and the expression of myelin basic protein in the hippocampus was down-regulated in the model group compared with the control group.All the above indexes were ameliorated in the aminooxyacetic acid remedy group compared with the model group.These findings indicate that aminooxyacetic acid can improve learning and memory in a chronic alcoholism rat model,which may be associated with reduction of hippocampal H2S level and mitochondrial ATPase activity,and up-regulation of myelin basic protein levels in the hippocampus.展开更多
Background:Multiple mitochondrial dysfunction syndromes(MMDS)presents as complex mitochondrial damage,thus impairing a variety of metabolic pathways.Heart dysplasia has been reported in MMDS patients;however,the speci...Background:Multiple mitochondrial dysfunction syndromes(MMDS)presents as complex mitochondrial damage,thus impairing a variety of metabolic pathways.Heart dysplasia has been reported in MMDS patients;however,the specific clinical symptoms and pathogenesis remain unclear.More urgently,there is a lack of an animal model to aid research.Therefore,we selected a reported MMDS causal gene,Isca1,and established an animal model of MMDS complicated with cardiac dysplasia.Methods:The myocardium-specific Isca1 knockout heterozygote(Isca1 HET)rat was obtained by crossing the Isca1 conditional knockout(Isca1 cKO)rat with theαmyosin heavy chain Cre(α-MHC-Cre)rat.Cardiac development characteristics were determined by ECG,blood pressure measurement,echocardiography and histopatho-logical analysis.The responsiveness to pathological stimuli were observed through adriamycin treatment.Mitochondria and metabolism disorder were determined by activity analysis of mitochondrial respiratory chain complex and ATP production in myocardium.Results:ISCA1 expression in myocardium exhibited a semizygous effect.Isca1 HET rats exhibited dilated cardiomyopathy characteristics,including thin-walled ventri-cles,larger chambers,cardiac dysfunction and myocardium fibrosis.Downregulated ISCA1 led to deteriorating cardiac pathological processes at the global and organiza-tional levels.Meanwhile,HET rats exhibited typical MMDS characteristics,including damaged mitochondrial morphology and enzyme activity for mitochondrial respira-tory chain complexesⅠ,ⅡandⅣ,and impaired ATP production.Conclusion:We have established a rat model of MMDS complicated with cardiomyopathy,it can also be used as model of myocardial energy metabolism dysfunction and mitochondrial cardiomyopathy.This model can be applied to the study of the mechanism of energy metabolism in cardiovascular diseases,as well as research and development of drugs.展开更多
BACKGROUND There is still no consensus on which concentration of mesenchymal stem cells(MSCs)to use for promoting fracture healing in a rat model of long bone fracture.AIM To assess the optimal concentration of MSCs f...BACKGROUND There is still no consensus on which concentration of mesenchymal stem cells(MSCs)to use for promoting fracture healing in a rat model of long bone fracture.AIM To assess the optimal concentration of MSCs for promoting fracture healing in a rat model.METHODS Wistar rats were divided into four groups according to MSC concentrations:Normal saline(C),2.5×10^(6)(L),5.0×10^(6)(M),and 10.0×10^(6)(H)groups.The MSCs were injected directly into the fracture site.The rats were sacrificed at 2 and 6 wk post-fracture.New bone formation[bone volume(BV)and percentage BV(PBV)]was evaluated using micro-computed tomography(CT).Histological analysis was performed to evaluate fracture healing score.The protein expression of factors related to MSC migration[stromal cell-derived factor 1(SDF-1),transforming growth factor-beta 1(TGF-β1)]and angiogenesis[vascular endothelial growth factor(VEGF)]was evaluated using western blot analysis.The expression of cytokines associated with osteogenesis[bone morphogenetic protein-2(BMP-2),TGF-β1 and VEGF]was evaluated using real-time polymerase chain reaction.RESULTS Micro-CT showed that BV and PBV was significantly increased in groups M and H compared to that in group C at 6 wk post-fracture(P=0.040,P=0.009;P=0.004,P=0.001,respectively).Significantly more cartilaginous tissue and immature bone were formed in groups M and H than in group C at 2 and 6 wk post-fracture(P=0.018,P=0.010;P=0.032,P=0.050,respectively).At 2 wk post fracture,SDF-1,TGF-β1 and VEGF expression were significantly higher in groups M and H than in group L(P=0.031,P=0.014;P<0.001,P<0.001;P=0.025,P<0.001,respectively).BMP-2 and VEGF expression were significantly higher in groups M and H than in group C at 6 wk postfracture(P=0.037,P=0.038;P=0.021,P=0.010).Compared to group L,TGF-β1 expression was significantly higher in groups H(P=0.016).There were no significant differences in expression levels of chemokines related to MSC migration,angiogenesis and cytokines associated with osteogenesis between M and H groups at 2 and 6 wk post-fracture.CONCLUSION The administration of at least 5.0×10^(6)MSCs was optimal to promote fracture healing in a rat model of long bone fractures.展开更多
Objective： We have explored the role of nuclear factor kappa B（NF-κB） in the pathogenesis of chronic glomemlonephritis, and investigated the effect of rhododendron root on the activation of NF-κB. Methods： Thirt...Objective： We have explored the role of nuclear factor kappa B（NF-κB） in the pathogenesis of chronic glomemlonephritis, and investigated the effect of rhododendron root on the activation of NF-κB. Methods： Thirty-six Wistar rats were randomly divided into three groups： a control group, a glomerulonephritis model group and a therapy group（glomerulonephritis animals treated with the root of rhododendron）. Bovine serum albumin（BSA） nephritis was induced by subcutaneous immunization and daily intraperitoneal administration of BSA. Twenty-four-hour urinary protein and serum creatinine values were measured, and renal pathology was assessed histologically by optical microscopy and electron microscopy. NF-κB activity was determined by an electrophoretic mobility shift assay（EMSA）. Results：Compared with the control rats, glomerulonephritis model rats exhibited a significant increase in both 24 h urinary protein and serum creatinine, and had abnormal renal histology. The administration of the root of rhododendron ameliorated these changes. NF-κB activity in glomerulonephritis model group was greater than that in rhododendron-treated group, and NF-κB activity was greater in both glomerulonephritis groups than in the control group（P 〈 0.01）. Conclusion：These observations suggest that NF-κB plays a role in the pathogenesis of chronic glomemlonephritis, and rhododendron root may attenuate renal damages by downregulating the activation of NF- κB in this model.展开更多
Objective:To review treatment methods using natural extracts applied in rat models of periodontitis to establish a direction for the design of future experiments.Methods:An electronic search of PubMed was carried out ...Objective:To review treatment methods using natural extracts applied in rat models of periodontitis to establish a direction for the design of future experiments.Methods:An electronic search of PubMed was carried out using the keywords“periodontitis,”“natural”,“extracts”,“herb*”,“plants”and“rats.”Articles were screened against inclusion and exclusion criteria by two independent researchers.Data describing the characteristics of rats,method of periodontitis inducement,extract administration,and outcome measures were extracted and analyzed by more than two authors manually.Results:Of the 864 articles identified,33 studies were included.The use of SpragueeDawley rats(51.2%)and male rats(90.9%)was preferred.The most common experimental methods were ligature placement(72.7%)and oral administration(66.7%).Alveolar bone loss was evaluated mainly by photography(51.5%)and micro-computed tomography(39.4%).Factors related to bone remodeling and inflammatory processes,such as interleukin-1b,tumor necrosis factor-a,receptor activator of nuclear factor-kB,and osteoprotegerin,were also measured.Conclusion:Many diverse experimental periodontitis models have been used.However,few articles observed bone formation,immune responses,antibacterial effects,and toxicity.Future studies to assess natural extracts for the treatment of periodontitis should be robust and well-designed.展开更多
Melanins are widely used in medicine, pharmacology and cosmetics. Different technologies have been used to obtain melanin including： chemical synthesis based on oxidation of tyrosine and its derivatives; extraction f...Melanins are widely used in medicine, pharmacology and cosmetics. Different technologies have been used to obtain melanin including： chemical synthesis based on oxidation of tyrosine and its derivatives; extraction from animal materials; alkaline extraction from plant material; and microbiological synthesis. A few number of works have been published that were focused on purification of water insoluble 3,4-dihy- droxy-phenylalanine-melanins （Kukulianskaia et al., 2002）. The majority of synthetic and natural melanins are insoluble in wa- ter that significantly complicates preparation of pharmacolog- ical and cosmetic preparations. Obtaining of low-cost soluble biotechnological melanin can speed up application of melanin in medicine and other fields. For the first time, melanin-syn-thesizing strain with high level of pigment synthesis - Bacillus thuringiensis was obtained. The ecologically safe technology of biosynthesis, isolation and purification of the bacterial melanin has been elaborated.展开更多
OBJECTIVE:Ningdong granule is a traditional Chinese medicine preparation for the treatment of Tourette's syndrome.METHODS:Sixty-four rats were randomly assigned to a control group and three experimental groups,res...OBJECTIVE:Ningdong granule is a traditional Chinese medicine preparation for the treatment of Tourette's syndrome.METHODS:Sixty-four rats were randomly assigned to a control group and three experimental groups,respectively.Rat models of Tourette's syndrome were established via intraperitoneal injection of apomorphine(Apo).The rats in the experimental groups were subsequently intragastrically injected with haloperidol at 10 mg/kg(haloperidol group),Ningdong granule at 370 mg/kg(NDG group),and normal saline(0.9%) at 10 mL/kg(Apo group),respectively.Rat behaviors were observed and recorded on a daily basis.After 12 w,all rats were sacrificed,and sera and striatal tissues were harvested.Homovanillic acid levels in sera,as well as dopamine and dopamine D2 receptor mRNA expression in the striatum,were measured to determine possible mechanisms of Ningdong granule on the dopamine system in a rat model of Tourette's syndrome.RESULTS:Following intervention,stereotype actions of the Tourette's syndrome rats were significantly inhibited in the haloperidol and NDG groups,respectively(P<0.01).Homovanillic levels were significantly greater in the haloperidol and NDG groups,respectively(P<0.05).In addition,dopamine levels were significantly less in the NDG group(P<0.01),and DRD2 mRNA expression was significantly reduced in the haloperidol and NDG groups,respectively(P<0.05).CONCLUSION:Results demonstrated that Ningdong granule effectively inhibited stereotype actions and Tourette's syndrome symptoms by promoting dopamine metabolism,reducing dopamine levels in the striatum,increasing homovanillic acid content in sera,and reducing mRNA expression of DRD2 in the striatum.展开更多
BACKGROUND： Central adrenergic nerve and 5-serotonergic nerve can influence central cholinergic nerve on learning and memory and make easy for study; however, ginsenoside of stem and leaf （GSL） can improve function...BACKGROUND： Central adrenergic nerve and 5-serotonergic nerve can influence central cholinergic nerve on learning and memory and make easy for study; however, ginsenoside of stem and leaf （GSL） can improve functions of central adrenergic nerve; moreover, 5-serotonergic nerve and the combination with choline can produce synergistic effect and enhance learning and memory ability so as to improve learning and memory disorder of patients with Alzheimer disease （AD）. OBJECTIVE ： To observe the effects of GSL combining with choline on learning and memory of AD model rats DESIGN ： Randomized grouping design and controlled animal study SETIING ： Department of Pharmacology, Taishan Medical College MATERIALS ： The experiment was carried out in the Pharmacological Department of Medical College of Jilin University from October 1996 to January 1997. Forty healthy male Wistar rats of clean grade were randomly divided into 5 groups, including sham-injury group, model group, GSL group, choline group and combination group, with 8 rats in each group. Main medications： GSL with the volume more than 92.8% was provided by Department of Chemistry, Norman Bethune Medical College of Jilin University. Panaxatriol, the main component, was detected with thin layer scanning technique and regarded as the index of GSL quality [（55±1）%, CV= 2%, n = 5]. Choline was provided by the Third Shanghai Laboratory Factory. METHODS ： 150 nmol quinolinic acid was used to damage bilateral Meynert basal nuclei of adult rats so as to establish AD models. Rats in GSL, choline and combination groups were intragastric administrated with 400 mg/kg GSL, 200 mg/kg choline （20 mL/kg）, and both respectively last for 17 days starting from two days before operation. Rats in sham-injury group and model group were perfused with the same volume of distilled water once in each morning for the same days. （1） Passive avoidance step-down test： Five minutes later, rats jumped up safe platform when they were shocked with 36 V alternating current. If rats jumped down from the platform and the feet touched railings, the response was wrong. Numbers of wrong response were recorded within 3 minutes, and then the test was redone after 24 hours. （2） Morris water-maze spatial localization task： Swimming from jumping-off to platform directly was regarded as right response. Additionally, 4 successively right responses were regarded as the standard. Each rat was trained 10 times a day with 120 s per time for 3 successive days. The interval was 30 s. Three days later, numbers of right response were recorded. The training times were increased to 30 for unlearned rats. （3） Measurement of activity of choline acetylase in cerebral cortex： Rats were sacrificed at 17 days after operation to obtain cerebral cortex to measure activity of choline acetylase with radiochemistry technique. （4） Synergistic effect： It was expressed as Q value： Q value = factual incorporative effect/anticipant incorporative effect; Q ≥ 1 was regarded as synergistic effect. Anticipant incorporative effect = （EA＋EB-EA·EB）, EA and EB were single timing effect, respectively in GSL group and choline group. E（step-down test and Morris water maze test） = （x in model group - factual value in medicine groups）/x in model group; E （activity of choline acetylase） = （factual value in medicine groups -xin model group）/xin model group. MAIN OUTCOME MEASURES ： （1） Passive avoidance step-down test and Morris water-maze spatial localization task in the study of learning and memory; （2） activity of choline acetylase. RESULTS ： All 40 rats were involved in the final analysis. （1） Passive avoidance response： At learning phase on first day and retesting phase on the next day, numbers of wrong responses within 3 minutes were more in model group than sham operation group, and there was significant difference [（5.88±1.46）, （2.25±0.87） times; （2.63±1.06）, （0.50±0.53） times; P 〈 0.01]; numbers of wrong responses within 3 minutes were less in combination group than model group, and there was significant difference [learning phase： （1.12±0.83）, （5.88±1.46） times; retesting phase： （0.38±0.74）, （2.63±1.06）times, P 〈 0.01]; moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.07 and 1.59, respectively and it showed synergistic effect. Spatial localization task： Training times were more in model group than sham operation group, and there was significant difference [（2.9±2.5）, （12.6±3.5） times; P 〈 0.01]. Training times were less in combination group than model group, and there was significant difference [（11.8±2.4）, （27.9±2.5） times, P 〈 0.01]; moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.07 and it showed synergistic effect. （3） Activity of choline acetylase： Activity was lower in model group than sham operation group, and there was significant difference [（30.56±8.33）, （61.11 ±8.33） nkat/g; P 〈 0.01]. Activity was higher in combination group than model group and there was significant difference [（50.00±8.33）, （30.56±8.33） nkat/g, P 〈 0.01];moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.5 and it showed synergistic effect. CONCLUSZON： GSL in combination with choline can synergically improve the disorder of learning and memory of AD model rats. Its mechanism may be involved in enhancing the function of central cholinergic system.展开更多
AIM To efficiently replicate the biology and pathogenesis of human esophageal adenocarcinoma(EAC) using the modified Levrat model of end-to-side esophagojejunostomy. METHODS End-to-side esophagojejunostomy was perform...AIM To efficiently replicate the biology and pathogenesis of human esophageal adenocarcinoma(EAC) using the modified Levrat model of end-to-side esophagojejunostomy. METHODS End-to-side esophagojejunostomy was performed on rats to induce gastroduodenoesophageal reflux to develop EAC. Animals were randomly selected and serially euthanized at 10(n = 6),17(n = 8),24(n = 9),31(n = 6),38(n = 6),and 40(n = 6) wk postoperatively. The esophagi were harvested for downstream histopathology and gene expression. Histological evaluation wascompleted to determine respective rates of carcinogenic development. Quantitative reverse transcriptionpolymerase chain reaction was performed to determine gene expression levels of MUC2,CK19,and CK20,and results were compared to determine significant differences throughout disease progression stages.RESULTS The overall study mortality was 15%. Causes of mortality included anastomotic leak,gastrointestinal hemorrhage,stomach ulcer perforation,respiratory infection secondary to aspiration,and obstruction due to tumor or late anastomotic stricture. 10 wk following surgery,100% of animals presented with esophagitis. Barrett's esophagus(BE) was first observed at 10 wk,and was present in 100% of animals by 17 wk. Dysplasia was confirmed in 87.5% of animals at 17 wk,and increased to 100% by 31 wk. EAC was first observed in 44.4% of animals at 24 wk and increased to 100% by 40 wk. In addition,two animals at 38-40 wk post-surgery had confirmed macro-metastases in the lung/liver and small intestine,respectively. MUC2 gene expression was progressively down-regulated from BE to dysplasia to EAC. Both CK19 and CK20 gene expression significantly increased in a stepwise manner from esophagitis to EAC. CONCLUSION Esophagojejunostomy was successfully replicated in rats with low mortality and a high tumor burden,which may facilitate broader adoption to study EAC development,progression,and therapeutics.展开更多
The dopamine D1-D2 receptor agonist, R-apomorphine, has been shown to be neuroprotective in different models of Parkinson’s disease. Different mechanisms of action for this effect have been proposed, but not verified...The dopamine D1-D2 receptor agonist, R-apomorphine, has been shown to be neuroprotective in different models of Parkinson’s disease. Different mechanisms of action for this effect have been proposed, but not verified in the striatal 6-hydroxydopamine rat model. In this study, the expression of a set of genes involved in 1) signaling, 2) growth and differentiation, 3) neuronal regeneration and survival, 4) apoptosis and 5) inflammation in the striatum was measured after a subchronic R-apomorphine treatment (10 mg/kg/day, subcutaneously, during 11 days) in the striatal 6-hydroxydopamine rat model. The expression of 84 genes was analysed by using the rat neurotrophins and receptors RT2 ProfilerTM PCR array. The neuroprotective effects of R-apomorphine in the striatal 6-hydroxydopamine model were confirmed by neurochemical and behavioural analysis. The expression data suggest the observed neuroprotection involved the alteration of the gene and the protein expression levels of the anti-inflammatory corticotropin releasing hormone receptor (CRHR) 1 and the pro-inflammatory CRHR2 receptor confirming its potential anti-inflammatory action.展开更多
基金Correspondence:Christina Gertrude Yap,Jeffrey Cheah School of Medicine and Health Sciences,Monash University,Jalan Lagoon Selatan,Bandar Sunway,Subang Jaya 47500,Selangor,Malaysia.Email:christina.yap@monash.edu。
文摘This review focuses on rat models for studying the short-term and long-term effects of mild and severe hypoglycemia.We explored the physiological mechanisms to understand the consequences of hypoglycemia in rat experimental models.This study aims to investigate the therapeutic potential of phytotherapeutic agents and their efficacy in mitigating the adverse effects of hypoglycemia.Insights from our planned research will be beneficial in improving quality of life for individuals at risk of episodes of low blood sugar.Optimizing hypoglycemic rat models for research requires selecting a suitable experimental model that will be susceptible to hypoglycemia induction,effective monitoring of blood glucose levels,and maintaining a high survival rate throughout the required experimental duration.
基金National Key R&D Program of China,Grant/Award Number:2021YFC2502100,2023YFC3603404 and 2019YFA0111900The National Natural Science Foundation of China,Grant/Award Number:82072506,82272611 and 92268115+7 种基金The Hunan Provincial Science Fund for Distinguished Young Scholars,Grant/Award Number:2024JJ2089The Hunan Young Talents of Science and Technology,Grant/Award Number:2021RC3025The Provincial Clinical Medical Technology Innovation Project of Hunan,Grant/Award Number:2023SK2024 and 2020SK53709The Provincial Natural Science Foundation of Hunan,Grant/Award Number:2020JJ3060The National Natural Science Foundation of Hunan Province,Grant/Award Number:2023JJ30949The National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Grant/Award Number:2021KFJJ02 and 2021LNJJ05The Hunan Provincial Innovation Foundation for Postgraduate,Grant/Award Number:CX20230308 and CX20230312The Independent Exploration and Innovation Project for Postgraduate Students of Central South University,Grant/Award Number:2024ZZTS0163。
文摘Frozen shoulder(FS),also known as adhesive capsulitis,is a condition that causes contraction and stiffness of the shoulder joint capsule.The main symptoms are per-sistent shoulder pain and a limited range of motion in all directions.These symp-toms and poor prognosis affect people's physical health and quality of life.Currently,the specific mechanisms of FS remain unclear,and there is variability in treatment methods and their efficacy.Additionally,the early symptoms of FS are difficult to distinguish from those of other shoulder diseases,complicating early diagnosis and treatment.Therefore,it is necessary to develop and utilize animal models to under-stand the pathogenesis of FS and to explore treatment strategies,providing insights into the prevention and treatment of human FS.This paper reviews the rat models available for FS research,including external immobilization models,surgical internal immobilization models,injection modeling models,and endocrine modeling models.It introduces the basic procedures for these models and compares and analyzes the advantages,disadvantages,and applicability of each modeling method.Finally,our paper summarizes the common methods for evaluating FS rat models.
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.
基金supported by the Neurosurgery Pain Research Institute at Johns Hopkins University and by the Lehner Family Foundation.
文摘Chronic pain after spine surgery(CPSS)is a complex disorder characterized by multifactorial pathogenesis that occurs in 8%–40%of patients undergoing lumbar spine surgery.We aimed to develop a rat model that mimics clinical CPSS conditions by taking two sequential surgical procedures.Step 1:A plastic rod was inserted into the left L5 intervertebral foramen to produce a steady compression on the dorsal root ganglion(DRG)and the spinal nerve,a common cause of low back pain(LBP).Step 2:The rod was removed after 7 days when rats exhibited mechanical and heat hypersensitivity in the ipsilateral hindpaw,followed by a full L5 laminectomy to mimic spine decompression surgery in LBP patients.The retention of the rod induced a prolonged LBP-like behavior but was quickly resolved after rod removal without laminectomy.However,rats that received laminectomy after rod removal developed heightened mechanical and heat sensitivity in the hindpaw,impaired gait,and reduced spontaneous exploration activity,indicating CPSS.Patch clamp recording revealed a significant augmentation in the intrinsic excitability of smalldiameter DRG neurons in CPSS rats.Administration of Dermorphin[D-Arg2,Lys4](1–4)amide(DALDA,5mg/kg,i.p.),a peripherally acting mu-opioid receptor(MOR)-preferred agonist,attenuated pain hypersensitivity,capsaicin-induced[Ca^(2+)]i rising and the increased intrinsic excitability of DRG neurons from CPSS rats.Our findings suggest that this new model,which mirrors the nature of CPSS developed in patients,may be useful for future studies of the underlying mechanisms.
文摘AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential stress.METHODS Animal pups were divided into two groups from postnatal day 2: controls and the sequential-stress-treated. The sequential-stress-treated group received maternal separation and acute gastric irritation early in life and restraint stress in adulthood; controls were reared undisturbed with their mothers. Rats in both groups were followed to adulthood(8 wk) at which point the anxietylike behaviors and visceromotor responses to gastric distention(20-100 mm Hg) and gastric emptying were tested. Meanwhile, alterations in several anxiety-related brain-stomach modulators including 5-hydroxytryptamine(5-HT), γ-aminobutyric acid(GABA), brain-derived neurotrophic factor(BDNF) and nesfatin-1 in the rat hippocampus, plasma and gastric fundus and the 5-HT1 A receptor(5-HT1 AR) in the hippocampal CA1 subfield and the mucosa of the gastric fundus were examined.RESULTS Sequential-stress-treated rats simultaneously demonstrated anxiety-like behaviors and GHS in dose-dependent manner compared with the control group. Although rats in both groups consumed similar amount of solid food, the rate of gastric emptying was lower in the sequentialstress-treated rats than in the control group. Sequential stress significantly decreased the levels of 5-HT(51.91 ± 1.88 vs 104.21 ± 2.88, P < 0.01), GABA(2.38 ± 0.16 vs 5.01 ± 0.13, P < 0.01) and BDNF(304.40 ± 10.16 vs 698.17 ± 27.91, P < 0.01) in the hippocampus but increased the content of nesfatin-1(1961.38 ± 56.89 vs 1007.50 ± 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT(47.82 ± 2.29 vs 89.45 ± 2.61, P < 0.01) and BDNF(257.05 ± 12.89 vs 536.71 ± 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it(1391.75 ± 42.77 vs 737.88 ± 33.15, P < 0.01); significantly decreased the levels of 5-HT(41.15 ± 1.81 vs 89.17 ± 2.31, P < 0.01) and BDNF(226.49 ± 12.10 vs 551.36 ± 16.47, P < 0.01) in the gastric fundus but increased the content of nesfatin-1 in the same site(1534.75 ± 38.52 vs 819.63 ± 38.04, P < 0.01). The expressions of 5-HT1 AR in the hippocampal CA1 subfield and the mucosa of the gastric fundus were down-regulated measured by IHC(Optical Density value: Hippocampus 15253.50 ± 760.35 vs 21149.75 ± 834.13; gastric fundus 15865.25 ± 521.24 vs 23865.75 ± 1868.60; P < 0.05, respectively) and WB(0.38 ± 0.01 vs 0.57 ± 0.03, P < 0.01)(n = 8 in each group). CONCLUSION Sequential stress could induce a potential rat model of anxiety-like GHS of FD, which could be used to research the mechanisms of this intractable disease.
基金Supported by National Natural Science Foundation of China(No.81100681)
文摘AIM:To develop a reliable,reproducible rat model of retinal vein occlusion(RVO)with a novel photosensitizer(erythrosin B)and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in adult male rats via photochemically-induced ischemia.Retinal changes were monitored via color fundus photography and fluorescein angiography at 1 and 3h,and 1,4,7,14,and 21d after irradiation.Tissue slices were evaluated histopathologically.Retinal ganglion cell survival at different times after RVO induction was quantified by nuclear density count.Retinal thickness was also observed.RESULTS:For all rats in both the central and branch RVO groups,blood flow ceased immediately after laser irradiation and retinal edema was evident at one hour.The retinal detachment rate was 100%at 3h and developed into bullous retinal detachment within 24h.Retinal hemorrhages were not observed until 24h.Clearance of the occluded veins at 7d was observed by fluorescein angiography.Disease manifestation in the central RVO eyes was more severe than in the branch RVO group.A remarkable reduction in the ganglion cell count and retinal thickness was observed in the central RVO group by 21d,whereas moderate changes occurred in the branch RVO group.CONCLUSION:Rat RVO created by photochemicallyinduced ischemia using erythrosin B is a reproducible and reliable animal model for mimicking the key features of human RVO.However,considering the 100%rate ofretinal detachment,this animal model is more suitable for studying RVO with chronic retinal detachment.
基金Supported by Hungarian Scientific Research Fund,No.OTKA PD 108309(to Bódi N)European Union and the State of Hungaryco-financed by the European Social Fund in the frame-work of TáMOP 4.2.4.A/2-11/1-2012-0001"National Excellence Program"
文摘AIM:To establish a rat model suitable to investigate the repetitive relapsing inflammations(RRI)characteristic to Crohn’s disease.METHODS:Colitis was induced by 2,4,6-trinitrobenzenesulfonic acid(TNBS).RRI were mimicked by repeating administrations of TNBS.Tissue samples were taken from control,once,twice and three times treated rats from the inflamed and adjacent non-inflamed colonic segments at different timepoints during the acute intestinal inflammation.The means of the ulcerated area were measured to evaluate the macroscopic mu-cosal damage.The density of myenteric neurons was determined on whole mounts by Hu C/Hu D immunohistochemistry.Heme oxygenase-1(HO-1)expression was evaluated by molecular biological techniques.RESULTS:TNBS-treated rats displayed severe colitis,but the mortality was negligible,and an increase of body weight was characteristic throughout the experimental period.The widespread loss of myenteric neurons,and marked but transient HO-1 up-regulation were demonstrated after the first TNBS administration.After repeated doses the length of the recovery time and extent of the ulcerous colonic segments were markedly decreased,and the neuronal loss was on a smaller scale and was limited to the inflamed area.HO-1 m RNA level was notably greater than after a single dose and overexpression was sustained throughout the timepoints examined.Nevertheless,the HO-1protein up-regulation after the second TNBS treatment proved to be transient.Following the third treatment HO-1 protein expression could not be detected.CONCLUSION:Experimentally provoked RRI may exert a protective preconditioning effect against the mucosal and neuronal damage.The persistent up-regulation of HO-1 m RNA expression may correlate with this.
基金supported by The Beljanski Foundation(to JY)and Military Laboratory Animal Fund(Grant No.SYDW[2017]15to TF)。
文摘Objective:Herbal medicine is an important therapeutic option for benign prostatic hyperplasia(BPH),a common disease in older men that can seriously affect their quality of life.Currently,it is crucial to develop agents with strong efficacy and few side effects.Herein we investigated the effects of the extract of Rauwolfia vomitoria,a shrub grown in West Africa,on BPH.Methods:Rats with testosterone-induced BPH were treated with R.vomitoria.Prostates were histologically analyzed by Hematoxylin and eosin staining.Proliferation index and the expression levels of androgen receptor and its associated proteins were quantified through immunohistochemistry and immunoblotting.Androgen receptor target genes were examined by quantitative real-time polymerase chain reaction.The sperm count and body weight of rats were also measured.Results:The oral administration of R.vomitoria extract significantly reduced the prostate weight and prostate weight index in BPH rats,supported by the decreased thickness of the prostate epithelial layer and increased lumen size.Similar effects were observed in the BPH rats treated with the reference drug,finasteride.R.vomitoria extract significantly reduced the testosterone-induced proliferation markers,including proliferating cell nuclear antigen and cyclin D1,in the prostate glands of BPH rats;it also reduced levels of androgen receptor,its associated protein steroid 5 a-reductase 1 and its downstream target genes(FK506-binding protein 5 and matrix metalloproteinase 2).Notably,compared with the finasteride group,R.vomitoria extract did not significantly reduce sperm count.Conclusion:R.vomitoria suppresses testosterone-induced BPH development.Due to its milder side effects,R.vomitoria could be a promising therapeutic agent for BPH.
基金Supported by Spanish Ministry of Health and Consumer Affairs,No.PI060305
文摘AIM To establish a rat model of anal sphincter injury and test different systems to provide stem cells to injured area.METHODS Adipose-derived stem cells(ASCs)were isolated from BDIX rats and were transfected with green fluorescent protein(GFP)for cell tracking.Biosutures(sutures covered with ASCs)were prepared with 1.5×10~6 GFPASCs,and solutions of 10~6 GFP-ASCs in normal saline were prepared for injection.Anorectal normal anatomy was studied on Wistar and BDIX female rats.Then,we designed an anal sphincter injury model consisting of a 1-cm extra-mucosal miotomy beginning at the anal verge in the anterior middle line.The sphincter lesion was confirmed with conventional histology(hematoxylin and eosin)and immunofluorescence with 4',6-diamidino-2-phenylindole(commonly known as DAPI),GFP andα-actin.Functional effect was assessed with basal anal manometry,prior to and after injury.After sphincter damage,36 BDIX rats were randomized to three groups for:(1)Cell injection without repair;(2)biosuture repair;and(3)conventional suture repair and cell injection.Functional and safety studies were conducted on all the animals.Rats were sacrificed after 1,4 or 7 d.Then,histological and immunofluorescence studies were performed on the surgical area.RESULTS With the described protocol,biosutures had been covered with at least 820000-860000 ASCs,with 100%viability.Our studies demonstrated that some ASCs remained adhered after suture passage through the muscle.Morphological assessment showed that the rat anal anatomy is comparable with human anatomy;two sphincters are present,but the external sphincter is poorly developed.Anal sphincter pressure data showed spontaneous,consistent,rhythmic anal contractions,taking the form of"plateaus"with multiple twitches(peaks)in each pressure wave.These basal contractions were very heterogeneous;their frequency was 0.91-4.17 per min(mean 1.6980,SD 0.57698),their mean duration was 26.67 s and mean number of peaks was 12.53.Our morphological assessment revealed that with the aforementioned surgical procedure,both sphincters were completely sectioned.In manometry,the described activity disappeared and was replaced by a gentle oscillation of basal line,without a recognizable pattern.Surprisingly,these findings appeared irrespective of injury repair or not.ASCs survived in this potentially septic area for 7 d,at least.We were able to identify them in 84%of animals,mainly in the muscular section area or in the tissue between the muscular endings.ASCs formed a kind of"conglomerate"in rats treated with injections,while in the biosuture group,they wrapped the suture.ASCs were also able to migrate to the damaged zone.No relevant adverse events or mortality could be related to the stem cells in our study.We also did not find unexpected tissue growths.CONCLUSION The proposed procedure produces a consistent sphincter lesion.Biosutures and injections are suitable for cell delivery.ASCs survive and are completely safe in this clinical setting.
基金Supported by the Chinese National Natural Science Foundation,No.81471719
文摘AIM To develop a novel rat model of heterogeneous hepatic injury.METHODS Seventy male Sprague-Dawley rats were randomly divided into a control group(n = 10) and a colchicine group(n =60). A 0.25% colchicine solution(0.4 mL/kg) was injected via the splenic vein in the colchicine group to develop a rat model of heterogeneous hepatic injury. An equal volume of normal saline was injected via the splenic vein in the control group. At days 3, 7, and 14 and weeks 4, 8, and 12 after the operation, at least seven rats of the colchicine group were selected randomly for magnetic resonance imaging(MRI) examinations, and then they were euthanized. Ten rats of the control group underwent MRI examinations at the same time points, and then were euthanized at week 12. T2-weighted images(T2 WI) and diffusion weighted imaging(DWI) were used to evaluate the heterogeneous hepatic injury. The heterogeneous injury between the left and right hepatic lobes was assessed on liver sections according to the histological scoring criteria, and correlated with the results of MRI study. RESULTS Obvious pathological changes occurred in the hepatic parenchyma in the colchicine group. Hepatic injury scores were significantly different between the left and right lobes at each time point(P < 0.05). There was a significant difference in apparent diffusion coefficient(ADC) of DWI and liver-to-muscle ratio(LMR) of T2 WI between the left and right lobes of rats in the colchicine group(P < 0.05) at each time point, and similar results were observed between the colchicine and control groups. Besides, there was a significant correlation between hepatic injury scores and ADC values or LMR(r =-0.682, P = 0.000; r =-0.245, P = 0.018).CONCLUSION Injection with colchicine via the splenic vein can be used to successfully develop a rat model of heterogeneous hepatic injury. DWI and T2 WI may help evaluate the heterogeneous injury among liver lobes.
基金supported by the National Natural Science Foundation of China(to YMX),No.81530037,81471158a grant from the Department of Education of Henan Province of China(to ALD),No.15A310006
文摘Chronic alcoholism seriously damages the central nervous system and leads to impaired learning and memory.Cell damage in chronic alcoholism is strongly associated with elevated levels of hydrogen sulfide（H2S） and calcium ion overload.Aminooxyacetic acid is a cystathionine-β-synthase activity inhibitor that can reduce H2S formation in the brain.This study sought to observe the effect of aminooxyacetic acid on learning and memory in a chronic alcoholism rat model.Rats were randomly divided into three groups.Rats in the control group were given pure water for 28 days.Rats in the model group were given 6% alcohol for 28 days to establish an alcoholism rat model.Rats in the aminooxyacetic acid remedy group were also given 6% alcohol for 28 days and were also intraperitoneally injected daily with aminooxyacetic acid（5 mg/kg） from day 15 to day 28.Learning and memory was tested using the Morris water maze test.The ultrastructure of mitochondria in the hippocampus was observed by electron microscopy.H2S levels in the hippocampus were measured indirectly by spectrophotometry,and ATPase activity was measured using a commercial kit.The expression of myelin basic protein was determined by immunohistochemistry and western blotting.Compared with the control group,latency and swimming distance were prolonged in the navigation test on days 2,3,and 4 in the model group.In the spatial probe test on day 5,the number of platform crosses was reduced in the model group.Cristae cracks,swelling or deformation of mitochondria appeared in the hippocampus,the hippocampal H2S level was increased,the mitochondrial ATPase activity was decreased,and the expression of myelin basic protein in the hippocampus was down-regulated in the model group compared with the control group.All the above indexes were ameliorated in the aminooxyacetic acid remedy group compared with the model group.These findings indicate that aminooxyacetic acid can improve learning and memory in a chronic alcoholism rat model,which may be associated with reduction of hippocampal H2S level and mitochondrial ATPase activity,and up-regulation of myelin basic protein levels in the hippocampus.
基金The present work was supported in part by the Beijing Natural Science Foundation(5212017)CAMS Innovation Fund for Medical Sciences(CIFMS,2016-I2M-1-015)National Natural Science Foundation(31872314 and 31970508).
文摘Background:Multiple mitochondrial dysfunction syndromes(MMDS)presents as complex mitochondrial damage,thus impairing a variety of metabolic pathways.Heart dysplasia has been reported in MMDS patients;however,the specific clinical symptoms and pathogenesis remain unclear.More urgently,there is a lack of an animal model to aid research.Therefore,we selected a reported MMDS causal gene,Isca1,and established an animal model of MMDS complicated with cardiac dysplasia.Methods:The myocardium-specific Isca1 knockout heterozygote(Isca1 HET)rat was obtained by crossing the Isca1 conditional knockout(Isca1 cKO)rat with theαmyosin heavy chain Cre(α-MHC-Cre)rat.Cardiac development characteristics were determined by ECG,blood pressure measurement,echocardiography and histopatho-logical analysis.The responsiveness to pathological stimuli were observed through adriamycin treatment.Mitochondria and metabolism disorder were determined by activity analysis of mitochondrial respiratory chain complex and ATP production in myocardium.Results:ISCA1 expression in myocardium exhibited a semizygous effect.Isca1 HET rats exhibited dilated cardiomyopathy characteristics,including thin-walled ventri-cles,larger chambers,cardiac dysfunction and myocardium fibrosis.Downregulated ISCA1 led to deteriorating cardiac pathological processes at the global and organiza-tional levels.Meanwhile,HET rats exhibited typical MMDS characteristics,including damaged mitochondrial morphology and enzyme activity for mitochondrial respira-tory chain complexesⅠ,ⅡandⅣ,and impaired ATP production.Conclusion:We have established a rat model of MMDS complicated with cardiomyopathy,it can also be used as model of myocardial energy metabolism dysfunction and mitochondrial cardiomyopathy.This model can be applied to the study of the mechanism of energy metabolism in cardiovascular diseases,as well as research and development of drugs.
基金the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea,No.HI20C1405。
文摘BACKGROUND There is still no consensus on which concentration of mesenchymal stem cells(MSCs)to use for promoting fracture healing in a rat model of long bone fracture.AIM To assess the optimal concentration of MSCs for promoting fracture healing in a rat model.METHODS Wistar rats were divided into four groups according to MSC concentrations:Normal saline(C),2.5×10^(6)(L),5.0×10^(6)(M),and 10.0×10^(6)(H)groups.The MSCs were injected directly into the fracture site.The rats were sacrificed at 2 and 6 wk post-fracture.New bone formation[bone volume(BV)and percentage BV(PBV)]was evaluated using micro-computed tomography(CT).Histological analysis was performed to evaluate fracture healing score.The protein expression of factors related to MSC migration[stromal cell-derived factor 1(SDF-1),transforming growth factor-beta 1(TGF-β1)]and angiogenesis[vascular endothelial growth factor(VEGF)]was evaluated using western blot analysis.The expression of cytokines associated with osteogenesis[bone morphogenetic protein-2(BMP-2),TGF-β1 and VEGF]was evaluated using real-time polymerase chain reaction.RESULTS Micro-CT showed that BV and PBV was significantly increased in groups M and H compared to that in group C at 6 wk post-fracture(P=0.040,P=0.009;P=0.004,P=0.001,respectively).Significantly more cartilaginous tissue and immature bone were formed in groups M and H than in group C at 2 and 6 wk post-fracture(P=0.018,P=0.010;P=0.032,P=0.050,respectively).At 2 wk post fracture,SDF-1,TGF-β1 and VEGF expression were significantly higher in groups M and H than in group L(P=0.031,P=0.014;P<0.001,P<0.001;P=0.025,P<0.001,respectively).BMP-2 and VEGF expression were significantly higher in groups M and H than in group C at 6 wk postfracture(P=0.037,P=0.038;P=0.021,P=0.010).Compared to group L,TGF-β1 expression was significantly higher in groups H(P=0.016).There were no significant differences in expression levels of chemokines related to MSC migration,angiogenesis and cytokines associated with osteogenesis between M and H groups at 2 and 6 wk post-fracture.CONCLUSION The administration of at least 5.0×10^(6)MSCs was optimal to promote fracture healing in a rat model of long bone fractures.
文摘Objective： We have explored the role of nuclear factor kappa B（NF-κB） in the pathogenesis of chronic glomemlonephritis, and investigated the effect of rhododendron root on the activation of NF-κB. Methods： Thirty-six Wistar rats were randomly divided into three groups： a control group, a glomerulonephritis model group and a therapy group（glomerulonephritis animals treated with the root of rhododendron）. Bovine serum albumin（BSA） nephritis was induced by subcutaneous immunization and daily intraperitoneal administration of BSA. Twenty-four-hour urinary protein and serum creatinine values were measured, and renal pathology was assessed histologically by optical microscopy and electron microscopy. NF-κB activity was determined by an electrophoretic mobility shift assay（EMSA）. Results：Compared with the control rats, glomerulonephritis model rats exhibited a significant increase in both 24 h urinary protein and serum creatinine, and had abnormal renal histology. The administration of the root of rhododendron ameliorated these changes. NF-κB activity in glomerulonephritis model group was greater than that in rhododendron-treated group, and NF-κB activity was greater in both glomerulonephritis groups than in the control group（P 〈 0.01）. Conclusion：These observations suggest that NF-κB plays a role in the pathogenesis of chronic glomemlonephritis, and rhododendron root may attenuate renal damages by downregulating the activation of NF- κB in this model.
基金supported by Kyung Hee University(Seoul,Republic of Korea)in 2018(KHU-20180922).
文摘Objective:To review treatment methods using natural extracts applied in rat models of periodontitis to establish a direction for the design of future experiments.Methods:An electronic search of PubMed was carried out using the keywords“periodontitis,”“natural”,“extracts”,“herb*”,“plants”and“rats.”Articles were screened against inclusion and exclusion criteria by two independent researchers.Data describing the characteristics of rats,method of periodontitis inducement,extract administration,and outcome measures were extracted and analyzed by more than two authors manually.Results:Of the 864 articles identified,33 studies were included.The use of SpragueeDawley rats(51.2%)and male rats(90.9%)was preferred.The most common experimental methods were ligature placement(72.7%)and oral administration(66.7%).Alveolar bone loss was evaluated mainly by photography(51.5%)and micro-computed tomography(39.4%).Factors related to bone remodeling and inflammatory processes,such as interleukin-1b,tumor necrosis factor-a,receptor activator of nuclear factor-kB,and osteoprotegerin,were also measured.Conclusion:Many diverse experimental periodontitis models have been used.However,few articles observed bone formation,immune responses,antibacterial effects,and toxicity.Future studies to assess natural extracts for the treatment of periodontitis should be robust and well-designed.
文摘Melanins are widely used in medicine, pharmacology and cosmetics. Different technologies have been used to obtain melanin including： chemical synthesis based on oxidation of tyrosine and its derivatives; extraction from animal materials; alkaline extraction from plant material; and microbiological synthesis. A few number of works have been published that were focused on purification of water insoluble 3,4-dihy- droxy-phenylalanine-melanins （Kukulianskaia et al., 2002）. The majority of synthetic and natural melanins are insoluble in wa- ter that significantly complicates preparation of pharmacolog- ical and cosmetic preparations. Obtaining of low-cost soluble biotechnological melanin can speed up application of melanin in medicine and other fields. For the first time, melanin-syn-thesizing strain with high level of pigment synthesis - Bacillus thuringiensis was obtained. The ecologically safe technology of biosynthesis, isolation and purification of the bacterial melanin has been elaborated.
基金supported by a grant from Binzhou Medical University (NO. BY2010KYQD13)
文摘OBJECTIVE:Ningdong granule is a traditional Chinese medicine preparation for the treatment of Tourette's syndrome.METHODS:Sixty-four rats were randomly assigned to a control group and three experimental groups,respectively.Rat models of Tourette's syndrome were established via intraperitoneal injection of apomorphine(Apo).The rats in the experimental groups were subsequently intragastrically injected with haloperidol at 10 mg/kg(haloperidol group),Ningdong granule at 370 mg/kg(NDG group),and normal saline(0.9%) at 10 mL/kg(Apo group),respectively.Rat behaviors were observed and recorded on a daily basis.After 12 w,all rats were sacrificed,and sera and striatal tissues were harvested.Homovanillic acid levels in sera,as well as dopamine and dopamine D2 receptor mRNA expression in the striatum,were measured to determine possible mechanisms of Ningdong granule on the dopamine system in a rat model of Tourette's syndrome.RESULTS:Following intervention,stereotype actions of the Tourette's syndrome rats were significantly inhibited in the haloperidol and NDG groups,respectively(P<0.01).Homovanillic levels were significantly greater in the haloperidol and NDG groups,respectively(P<0.05).In addition,dopamine levels were significantly less in the NDG group(P<0.01),and DRD2 mRNA expression was significantly reduced in the haloperidol and NDG groups,respectively(P<0.05).CONCLUSION:Results demonstrated that Ningdong granule effectively inhibited stereotype actions and Tourette's syndrome symptoms by promoting dopamine metabolism,reducing dopamine levels in the striatum,increasing homovanillic acid content in sera,and reducing mRNA expression of DRD2 in the striatum.
文摘BACKGROUND： Central adrenergic nerve and 5-serotonergic nerve can influence central cholinergic nerve on learning and memory and make easy for study; however, ginsenoside of stem and leaf （GSL） can improve functions of central adrenergic nerve; moreover, 5-serotonergic nerve and the combination with choline can produce synergistic effect and enhance learning and memory ability so as to improve learning and memory disorder of patients with Alzheimer disease （AD）. OBJECTIVE ： To observe the effects of GSL combining with choline on learning and memory of AD model rats DESIGN ： Randomized grouping design and controlled animal study SETIING ： Department of Pharmacology, Taishan Medical College MATERIALS ： The experiment was carried out in the Pharmacological Department of Medical College of Jilin University from October 1996 to January 1997. Forty healthy male Wistar rats of clean grade were randomly divided into 5 groups, including sham-injury group, model group, GSL group, choline group and combination group, with 8 rats in each group. Main medications： GSL with the volume more than 92.8% was provided by Department of Chemistry, Norman Bethune Medical College of Jilin University. Panaxatriol, the main component, was detected with thin layer scanning technique and regarded as the index of GSL quality [（55±1）%, CV= 2%, n = 5]. Choline was provided by the Third Shanghai Laboratory Factory. METHODS ： 150 nmol quinolinic acid was used to damage bilateral Meynert basal nuclei of adult rats so as to establish AD models. Rats in GSL, choline and combination groups were intragastric administrated with 400 mg/kg GSL, 200 mg/kg choline （20 mL/kg）, and both respectively last for 17 days starting from two days before operation. Rats in sham-injury group and model group were perfused with the same volume of distilled water once in each morning for the same days. （1） Passive avoidance step-down test： Five minutes later, rats jumped up safe platform when they were shocked with 36 V alternating current. If rats jumped down from the platform and the feet touched railings, the response was wrong. Numbers of wrong response were recorded within 3 minutes, and then the test was redone after 24 hours. （2） Morris water-maze spatial localization task： Swimming from jumping-off to platform directly was regarded as right response. Additionally, 4 successively right responses were regarded as the standard. Each rat was trained 10 times a day with 120 s per time for 3 successive days. The interval was 30 s. Three days later, numbers of right response were recorded. The training times were increased to 30 for unlearned rats. （3） Measurement of activity of choline acetylase in cerebral cortex： Rats were sacrificed at 17 days after operation to obtain cerebral cortex to measure activity of choline acetylase with radiochemistry technique. （4） Synergistic effect： It was expressed as Q value： Q value = factual incorporative effect/anticipant incorporative effect; Q ≥ 1 was regarded as synergistic effect. Anticipant incorporative effect = （EA＋EB-EA·EB）, EA and EB were single timing effect, respectively in GSL group and choline group. E（step-down test and Morris water maze test） = （x in model group - factual value in medicine groups）/x in model group; E （activity of choline acetylase） = （factual value in medicine groups -xin model group）/xin model group. MAIN OUTCOME MEASURES ： （1） Passive avoidance step-down test and Morris water-maze spatial localization task in the study of learning and memory; （2） activity of choline acetylase. RESULTS ： All 40 rats were involved in the final analysis. （1） Passive avoidance response： At learning phase on first day and retesting phase on the next day, numbers of wrong responses within 3 minutes were more in model group than sham operation group, and there was significant difference [（5.88±1.46）, （2.25±0.87） times; （2.63±1.06）, （0.50±0.53） times; P 〈 0.01]; numbers of wrong responses within 3 minutes were less in combination group than model group, and there was significant difference [learning phase： （1.12±0.83）, （5.88±1.46） times; retesting phase： （0.38±0.74）, （2.63±1.06）times, P 〈 0.01]; moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.07 and 1.59, respectively and it showed synergistic effect. Spatial localization task： Training times were more in model group than sham operation group, and there was significant difference [（2.9±2.5）, （12.6±3.5） times; P 〈 0.01]. Training times were less in combination group than model group, and there was significant difference [（11.8±2.4）, （27.9±2.5） times, P 〈 0.01]; moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.07 and it showed synergistic effect. （3） Activity of choline acetylase： Activity was lower in model group than sham operation group, and there was significant difference [（30.56±8.33）, （61.11 ±8.33） nkat/g; P 〈 0.01]. Activity was higher in combination group than model group and there was significant difference [（50.00±8.33）, （30.56±8.33） nkat/g, P 〈 0.01];moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.5 and it showed synergistic effect. CONCLUSZON： GSL in combination with choline can synergically improve the disorder of learning and memory of AD model rats. Its mechanism may be involved in enhancing the function of central cholinergic system.
基金Samantha Martin for providing statistical support
文摘AIM To efficiently replicate the biology and pathogenesis of human esophageal adenocarcinoma(EAC) using the modified Levrat model of end-to-side esophagojejunostomy. METHODS End-to-side esophagojejunostomy was performed on rats to induce gastroduodenoesophageal reflux to develop EAC. Animals were randomly selected and serially euthanized at 10(n = 6),17(n = 8),24(n = 9),31(n = 6),38(n = 6),and 40(n = 6) wk postoperatively. The esophagi were harvested for downstream histopathology and gene expression. Histological evaluation wascompleted to determine respective rates of carcinogenic development. Quantitative reverse transcriptionpolymerase chain reaction was performed to determine gene expression levels of MUC2,CK19,and CK20,and results were compared to determine significant differences throughout disease progression stages.RESULTS The overall study mortality was 15%. Causes of mortality included anastomotic leak,gastrointestinal hemorrhage,stomach ulcer perforation,respiratory infection secondary to aspiration,and obstruction due to tumor or late anastomotic stricture. 10 wk following surgery,100% of animals presented with esophagitis. Barrett's esophagus(BE) was first observed at 10 wk,and was present in 100% of animals by 17 wk. Dysplasia was confirmed in 87.5% of animals at 17 wk,and increased to 100% by 31 wk. EAC was first observed in 44.4% of animals at 24 wk and increased to 100% by 40 wk. In addition,two animals at 38-40 wk post-surgery had confirmed macro-metastases in the lung/liver and small intestine,respectively. MUC2 gene expression was progressively down-regulated from BE to dysplasia to EAC. Both CK19 and CK20 gene expression significantly increased in a stepwise manner from esophagitis to EAC. CONCLUSION Esophagojejunostomy was successfully replicated in rats with low mortality and a high tumor burden,which may facilitate broader adoption to study EAC development,progression,and therapeutics.
基金financial support of the Institute for the promotion of Innovation by Science and Technology in Flanders(IWT)(IWT420)National Fund for Scientific Research(FWO-Vlaanderen)(G.0071.05)and of the Research Council of the Vrije Universiteit Brusselresearch grant from the IWT(IWT420).
文摘The dopamine D1-D2 receptor agonist, R-apomorphine, has been shown to be neuroprotective in different models of Parkinson’s disease. Different mechanisms of action for this effect have been proposed, but not verified in the striatal 6-hydroxydopamine rat model. In this study, the expression of a set of genes involved in 1) signaling, 2) growth and differentiation, 3) neuronal regeneration and survival, 4) apoptosis and 5) inflammation in the striatum was measured after a subchronic R-apomorphine treatment (10 mg/kg/day, subcutaneously, during 11 days) in the striatal 6-hydroxydopamine rat model. The expression of 84 genes was analysed by using the rat neurotrophins and receptors RT2 ProfilerTM PCR array. The neuroprotective effects of R-apomorphine in the striatal 6-hydroxydopamine model were confirmed by neurochemical and behavioural analysis. The expression data suggest the observed neuroprotection involved the alteration of the gene and the protein expression levels of the anti-inflammatory corticotropin releasing hormone receptor (CRHR) 1 and the pro-inflammatory CRHR2 receptor confirming its potential anti-inflammatory action.
