胆汁酸受体TGR5对DSS诱导的小鼠结肠炎NF-κB通路的调节作用  

Regulation of NF-κB pathway by bile acid receptor TGR5 in DSS induced mouse colitis

作　　者：王宇豪 余晓云[2] 沈磊[1] WANG Yuhao;YU Xiaoyun;SHEN Lei(Department of Gastroenterology,Renmin Hospital of Wuhan University,Hubei Key Laboratory of Digestive System Disease,Wuhan 430060;Department of Gastroenterology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,China)

机构地区：[1]武汉大学人民医院消化内科消化系统疾病湖北省重点实验室,湖北武汉430060 [2]华中科技大学同济医学院附属协和医院消化内科

出　　处：《胃肠病学和肝病学杂志》2024年第11期1459-1463,共5页Chinese Journal of Gastroenterology and Hepatology

摘　　要：目的探究胆汁酸受体TGR5对DSS诱导的小鼠结肠炎的影响及对NF-κB通路的调节作用。方法选择24只体质量相近的C57BL/6小鼠,随机分为4组,每组各6只:对照组(正常饮水)、DSS模型组(2.5%DSS饮水造模)、DCA组(2.5%DSS饮水+33.3 g/L脱氧胆酸钠150μL灌肠)、TGR5抑制剂组(2.5%DSS饮水+33.3 g/L脱氧胆酸钠150μL灌肠+10 mmol/L×20μL SBI-115灌肠)。记录小鼠肠炎疾病活动指数(disease activity index,DAI)和结肠组织病理评分,RT-PCR检测小鼠结肠组织中的炎症因子IL-6、IL-17、TNF-α,Western blotting检测连接蛋白Occludin、p-CREB的蛋白表达及NF-κB通路中NF-κB p65蛋白的表达。结果与对照组相比,DSS模型组DAI评分和组织病理学评分更高(P<0.01),炎症因子IL-6、IL-17、TNF-α的表达升高(P<0.01),连接蛋白Occludin表达减少(P<0.01),NF-κB p65的蛋白表达水平上升(P<0.01),DCA组对上述改变有缓解作用(P<0.05),使用TGR5抑制剂后p-CREB的表达水平下降(P<0.01),且可以逆转DCA组的抑炎作用(P<0.05)。结论外源性脱氧胆酸可以激活胆汁酸受体TGR5并抑制NF-κB通路的激活从而减轻肠道炎症。Objective To investigate the effect of bile acid receptor TGR5 on DSS induced colitis in mice and its regulation of NF-κB pathway.Methods Twenty-four C57BL/6 mice with similar body weight were randomly divided into 4 groups with 6 mice in each group.Control group(normal drinking water),DSS model group(2.5%DSS drinking water modeling),DCA group(2.5%DSS drinking water+33.3 g/L sodium deoxycholate 150μL enema),TGR5 inhibitor group(2.5%DSS drinking water+33.3 g/L sodium deoxycholate 150μL enema+10 mmol/L×20μL SBI-115 enema).The disease activity index(DAI)and pathological score of colon were recorded,and the inflammatory factors IL-6,IL-17 and TNF-α in colon tissues of mice were detected by RT-PCR.Western blotting was used to detect the protein expression of Occludin,p-CREB and NF-κB p65 protein in NF-κB pathway.Results Compared with the control group,DAI score and histopathological score were higher than those in the DSS model group(P<0.01).The expression of inflammatory cytokines IL-6,IL-17 and TNF-α increased(P<0.01),the expression of Occludin decreased(P<0.01),and the expression level of NF-κB p65 was increased(P<0.01).DCA group had an alleviating effect on the above changes(P<0.05),the expression level of p-CREB in the TGR5 inhibitor group decreased(P<0.01)and reversed the anti-inflammatory effect of DCA group(P<0.05).Conclusion Exogenous deoxycholic acid can reduce intestinal inflammation by activating bile acid receptor TGR5 and inhibiting the activation of NF-κB pathway.

关 键 词：胆汁酸 TGR5 结肠炎 NF-ΚB通路 

分 类 号：R574[医药卫生—消化系统]