查看更多>>摘要：Background:A multitude of mouse models are utilized to emulate and study intestinal inflammation.T-cell receptor alpha chain (TCRα)-deficient mice are used as a model of spontaneous colitis that has similarities with human ulcerative colitis.However,colitis is triggered late in the life of the mouse (age:4-5 months),and inflammation does not develop at the same time in different mice.A previously conducted study reported that the administration of the drug piroxicam triggered predictable and early colitis in TCRα-deficient mice at the age of 6-8 weeks.However,a detailed characterization of ensuing inflammation was not provided.Methods:We conducted an in-depth examination of piroxicam-triggered colitis in TCRα-deficient mice,with emphasis on spatial histopathologic changes and analysis of expression of inflammatory markers.Furthermore,we tested amelioration of colitis with dexamethasone.Results:We confirmed that piroxicam induced a time-prescribed colitis and did so in the proximal colon as well as the cecum of TCRα-deficient mice.Piroxicam adminis-tration was observed to induce epithelial hyperplasia,goblet cell loss,and leukocyte infiltration with occasional ulceration.A Swiss roll technique was used to examine the colon and cecum in its entirety.Importantly,we observed that inflammation was mul-tifocal segmental,with areas of tissue damage in between healthy tissue.In addition,we observed variability in the severity of inflammation among replicate animals and treatments,and that the administration of dexamethasone only partially ameliorated inflammation in the proximal colon.Conclusions:Piroxicam consistently induced multifocal segmental colitis in the proxi-mal colon and cecum,although the degree of inflammation was reduced in the latter.Importantly,spatial variability in inflammation in the large intestine and the inter-replicate variation in the severity of inflammation must be taken into consideration when utilizing this murine model of synchronized colitis.
查看更多>>摘要：Background:Complementary medicine is an interesting field for extracting bio-active compounds from various plant and animal sources.The hepatoprotective effect of the methanolic extract of a species of sea cucumber called Holothuria leu-cospilota in an animal model of liver cancer caused by dimethyl nitrosamine (DMN) was studied.Methods:Wistar female rats were randomly divided into five groups ( n=12):control (intact),positive control (received 1% DMN[10 mg/kg/week,intraperitoneally]for 12 weeks),and three treatment groups (received 50,100,and 200 mg/kg/day H.leu-cospilota extract orally for 12 weeks along with intraperitoneal administration of 1% DMN[10 mg/kg/week]).In all groups,ultrasound was performed on the liver every week to check its density.Blood sampling and liver isolation were performed on three occasions,at 4,8,and 12 weeks,to check liver enzymes and the histopathological condition of the liver tissue (every week,four animals from each group were randomly selected).Results:Liver density changes were evident from the eighth week onward in the positive control group.Histopathological results indicated pathologic changes in the positive control group after 4 weeks.The increase in liver enzymes in the posi-tive control group was significantly different from that in the treatment and control groups.Conclusions:We demonstrated the hepatoprotective effect of H.leucospilota on DMN-induced liver damage in rats using biochemical and histological parameters and ultrasonography.More additional research (in silico or in vitro) is needed to find the exact mechanism and the main biological compound in H .leucospilota .
Victor Pascal-MoussellardEmilie BoucherStéphane TanguyPhilippe Cinquin...
553-561页
查看更多>>摘要：Background:Dihydrogen (H2 ) is produced endogenously by the intestinal microbiota through the fermentation of diet carbohydrates.Over the past few years,numer-ous studies have demonstrated the significant therapeutic potential of H2 in various pathophysiological contexts,making the characterization of its production in labora-tory species of major preclinical importance.Methods:This study proposes an innovative solution to accurately monitor H2 pro-duction in free-moving rodents while respecting animal welfare standards.The devel-oped device consisted of a wire rodent cage placed inside an airtight chamber in which the air quality was maintained,and the H2 concentration was continuously analyzed.After the airtightness and efficiency of the systems used to control and maintain air quality in the chamber were checked,tests were carried out on rats and mice with different metabolic phenotypes,over 12 min to 1-h experiments and repeatedly.H2 production rates (HPR) were obtained using an easy calculation algorithm based on a first-order moving average.Results:HPR in hyperphagic Zucker rats was found to be twice as high as in control Wistar rats,respectively,2.64 and 1.27 nmol.s-1 per animal.In addition,the ingestion of inulin,a dietary fiber,stimulated H2 production in mice.HPRs were 0.46 nmol.s-1 for animals under control diet and 1.99 nmol.s-1 for animals under inulin diet.Conclusions:The proposed device coupled with our algorithm enables fine analysis of the metabolic phenotype of laboratory rats or mice with regard to their endogenous H2 production.
查看更多>>摘要：Introduction:This study aimed to establish an animal model of open abdomen (OA) through temporary abdominal closure via different techniques.Methods:Adult male Sprague-Dawley rats were randomly divided into three groups:group A (OA with polypropylene mesh alone);group B (OA with polypro-pylene mesh combined with a patch);and group C (OA with polypropylene mesh and a sutured patch).Vital signs,pathophysiological changes,and survival rates were closely monitored in the rats for 7 days after surgery.Abdominal X-rays and histopathological examinations were performed to assess abdominal organ changes and wound healing.Results:The results showed no significant difference in mortality rates among the three groups ( p>0.05).However,rats in group B exhibited superior overall condi-tion,cleaner wounds,and a higher rate of wound healing compared to the other groups (p<0.05).Abdominal X-rays indicated that varying degrees of distal intestinal obstruction in all groups.Histopathological examinations revealed fibrous hyperpla-sia,inflammatory cell infiltration,neovascularization,and collagen deposition in all groups.Group B demonstrated enhanced granulation tissue generation,neovasculari-zation,and collagen deposition compared to the other groups ( p<0.05).Conclusions:Polypropylene mesh combined with patches is the most suitable method for establishing an animal model of OA.This model successfully replicated the patho-logical and physiological changes in postoperative patients with OA,specifically the progress of abdominal skin wound healing.It provides a practical and reliable animal model for OA research.
查看更多>>摘要：Background:Thromboelastography (TEG) is a widely utilized clinical testing method for real-time monitoring of platelet function and the thrombosis process.Lipid metab-olism disorders are crucial risk factors for thrombosis.The lipid metabolism charac-teristics of hamsters resemble those of humans more closely than mice and rats,and their relatively large blood volume makes them suitable for studying the mechanisms of thrombosis related to plasma lipid mechanisms.Whole blood samples from golden Syrian hamsters and healthy humans were obtained following standard clinical pro-cedures.TEG was employed to evaluate coagulation factor function,fibrinogen (Fib) function,platelet function,and the fibrinolytic system.Methods:The whole blood from hamster or healthy human was isolated following the clinical procedure,and TEG was employed to evaluate the coagulation factor func-tion,Fib function,platelet function,and fibrinolytic system.Coagulation analysis used ACLTOP750 automatic coagulation analysis pipeline.Blood routine testing used XN-2000 automatic blood analyzer.Results:TEG parameters revealed that hamsters exhibited stronger coagulation fac-tor function than humans (reaction time[R],p=0.0117),with stronger Fib function (alpha angle,p<0.0001;K-time[K],p<0.0001).Platelet function did not differ signifi-cantly (maximum amplitude[MA],p=0.077).Hamsters displayed higher coagulation status than humans (coagulation index[CI],p=0.0023),and the rate of blood clot dissolution in hamsters differed from that in humans (percentage lysis 30 min after MA,p=0.02).Coagulation analysis parameters indicated that prothrombin time (PT) and activated partial thromboplastin time (APTT) were faster in hamsters than in hu-mans (PT,p=0.0014;APTT,p=0.03),whereas the Fib content was significantly lower in hamsters than in humans ( p<0.0001).No significant difference was observed in thrombin time ( p=0.1949).Conclusions:In summary,TEG could be used to evaluate thrombosis and bleeding parameters in whole blood samples from hamsters.The platelet function of hamsters closely resembled that of humans,whereas their coagulation function was signifi-cantly stronger.
查看更多>>摘要：Background:The aim of this study was to investigate the influence of marking meth-ods on the outcomes of body composition analysis and provide guidance for the se-lection of marking methods in mouse body composition analysis.Methods:Male C57BL/6J mice aged 6 weeks were randomly assigned for pre-and post-ear tagging measurements.The body composition of the mice was measured using a small animal body composition analyzer,which provided measurements of the mass of fat,lean,and free fluid.Then,the mass of fat,lean and free fluid to body weight ratio was gained.Further data analysis was conducted to obtain the range and coeffi-cient of variation in body composition measurements for each mouse.The distribution of fat and lean tissue in the mice was also analyzed by comparing the fat-to-lean ratio.Results:(1) The mass of all body composition components in the ear tagging group was significantly lower than that in the control group.(2) There was a significant in-crease in the range and coefficient of variation of body composition measurements between the ear tagging group and the control group.(3) The fat-to-lean ratio in the ear tagging group was significantly lower than that in the control group.Conclusions:Ear tagging significantly lowered the results of body composition analy-sis in mice and higher the results of measurement error.Therefore,ear tagging should be avoided as much as possible when conducting body composition analysis experi-ments in mice.
查看更多>>摘要：Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to im-prove the immune compatibility between humans and pigs.Current knockout strat-egies are mainly aimed at the genes causing hyperacute immune rejection (HAR) that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure,in which process the MHC Ⅱ molecule plays critical roles.Methods:Thus,we generate a 4-gene ( GGTA1,CMAH,β4GalNT2,and CIITA ) knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously.Results:We successfully obtained 4KO piglets with deficiency in all alleles of genes,and at cellular and tissue levels.Additionally,the safety of our animals after gene editing was verified by using whole-genome sequencing and karyotyping.Piglets have survived for more than one year in the barrier,and also survived for more than 3 months in the conventional environment,suggesting that the piglets without MHC Ⅱ can be raised in the barrier and then gradually mated in the conventional environment.Conclusions:4KO piglets have lower immunogenicity,are safe in genomic level,and are easier to breed than the model with both MHC Ⅰ and Ⅱ deletion.
万方数据
维普