摘要
目的探讨γ-氨基丁酸(GABA)改善2,4,6-三硝基苯磺酸(TNBS)-乙醇诱导的结肠炎肠黏膜屏障损伤作用。方法 SD大鼠随机分为正常对照组,TNBS-乙醇溶液模型对照组,造模后GABA 200,100,50 mg·kg-1治疗组。造模后连续14 d,观察记录体质量变化、疾病活动指数(DAI);造模第15天,每组取5只,进行伊文思蓝染色。大鼠取结肠,组织学损伤评分,同时量取结肠长度、称重。通过WB法观察实验性结肠炎各组大鼠肠黏膜屏障连接蛋白及LC3表达情况。结果 GABA增加Caco-2细胞单层模型细胞电阻,减少FD4的渗透,降低单层模型通透性。GABA改善实验性结肠炎引起的体质量下降,增加DAI,降低结肠指数。另外,GABA降低实验性结肠炎大鼠伊文思蓝渗透性及结肠病理变化,显著提高大鼠Occludin、Claudin-4、ZO-1蛋白表达。实验性结肠炎大鼠肠细胞出现过度自噬,GABA抑制过度自噬。结论GABA通过改善肠黏膜屏障损伤,缓解TNBS-乙醇溶液诱导的实验性结肠炎,故改善肠黏膜屏障损伤可能是治疗炎症性肠病(IBD)的新方法。
Objective To investigate the protective effects of GABA against experimental inflammatory bowel disease( IBD) by enhanced intestinal barrier function and explore its underlying mechanisms. Methods Forty SD rats were randomly divided into normal control group,TNBS-alcohol model control group,200,100,50 mg · kg^-1 GABA treatment group. After modeling for 14 days,the changes of body weight and disease activity indexes( DAI) were observed. On the 15 th day after modeling,5 rats in each group were subjected to Evans blue staining. For the remaining rats,colon was collected and evaluated with histological injury score; the length and weight of the colon was determined.The intestinal mucosal barrier connexin and LC3 expression in rats with experimental colitis were observed by WB method. Results The cell resistance of Caco-2 monolayer models was increased and the infiltration of FD4 and the monolayer permeability was reduced by GABA.GABA also improved body mass,increased DAI,and lowered colon index. In addition,GABA decreased the Evans blue permeability and pathological changes in rats with experimental colitis,and significantly increased the Occludin,Claudin-4 and ZO-1 protein expression in the rats.Intestinal autophagy appeared in experimental colitis rats,GABA inhibited excessive autophagy. Conclusion GABA could relieve TNBS-ethanol-induced experimental colitis,and the mechanism might be related to the improvement of intestinal mucosal barrier injury.
作者
蒋廷媛
岳源
李芳华
JIANG Tingyuan;YUE Yuan;LI Fanghua(Department of Pharmacy,the Second People's Hospital of Yichang,Yichang 443000,China;School of Pharmaceutical Sciences,Wuhan University,Wuhan 430071,China)
出处
《医药导报》
CAS
北大核心
2018年第8期931-938,共8页
Herald of Medicine
基金
国家自然科学基金资助项目(81273523)
关键词
Γ-氨基丁酸
2
4
6-三硝基苯磺酸
炎症性肠病
肠黏膜屏障
Gamma-aminobutyric acid
2,4,6-trinitrobenzene sulfonic acid
Inflammatory bowel disease
Intestinal mucosal barrier