小鼠肠急性缺血再灌注模型中芳香烃受体活化对肠黏膜屏障功能的影响  

Effect of aryl hydrocarbon receptor activation on intestinal mucosal barrier in mice after acute intestinal ischemia reperfusion injury

作　　者：韩宾[1] 盛百伐 张治草[1] 蒲爱民[1] 殷久恒 杨桦[1] 

机构地区：[1]第三军医大学新桥医院普通外科,重庆400037

出　　处：《第三军医大学学报》2016年第10期1090-1095,共6页Journal of Third Military Medical University

基　　金：国家自然科学基金重点项目(813300335)~~

摘　　要：目的观察吲哚并[3,2-B]咔唑-6-甲醛[6-formylindolo(3,2-b)carbazole,FICZ]活化芳香烃受体(aryl hydrocarbon receptor,AhR)对C57BL/6小鼠肠急性缺血再灌注(I/R)后肠道屏障功能的影响。方法取C57BL/6小鼠18只,分成假手术组、I/R组和FICZ干预(I/R+FICZ)组,每组6只。小鼠肠I/R模型:肠系膜上动脉夹闭30 min,再灌注6 h。苏木精-伊红(HE)染色观察小肠组织形态学的变化。蛋白质印迹和免疫荧光检测观察肠黏膜AhR与ZO-1的表达与分布情况。结果与假手术组比较,I/R组肠黏膜明显肿胀,部分绒毛脱落、变粗,甚至倒伏、断裂,而I/R+FICZ组肠黏膜无明显肿胀,绒毛结构相对完整,形态接近正常;免疫荧光显示I/R后肠上皮表面ZO-1连续性明显破坏,而I/R+FICZ组肠上皮ZO-1连续性明显恢复。肠上皮蛋白定量分析显示:与假手术组比较,I/R组和I/R+FICZ组小鼠小肠上皮ZO-1表达分别下降50.7%和32.3%(P<0.05);I/R+FICZ组较I/R组小肠上皮ZO-1表达上调37.2%(P<0.05)。结论 FICZ预处理可有效缓解小鼠急性I/R对肠黏膜结构与功能的损伤,可能机制是上调ZO-1的表达。Objective To investigate the effect of aryl hydrocarbon receptor（ AhR） activation on the intestinal barrier function after acute intestinal ischemia reperfusion（ I / R） in a mouse model. Methods Eighteen 6-8-week-old C57 B L /6 mice were divided into 3 groups randomly,with 6 in each group： sham group,I / R group,and I / R ＋ 6-formylindolo（ 3,2-b） carbazole（ FICZ） group. The mouse intestinal I / R model was established by mechanically blocking the superior mesenteric artery（ SMA） temporarily for 30 min,following by reperfusion for 6 h. Histological changes in the small intestine were observed by hematoxylin-eosin staining（ HE）. The protein expression of AhR and tight junction protein ZO-1 in the intestine epithelium was detected by immunofluorescence assay and Western blotting. Results Both HE staining and immunofluorescence assay indicated the integrate intestinal villi with continuous ZO-1 expression on the surface of the villi alone in the sham group. The intestinal villi of the I / R group were partially dissociated,thickened,and fractured,meanwhile the destroyed continuity of ZO-1 turned up on the top of the villi. The intestinal villi of the I / R ＋ FICZ group were neatly arranged and the damage to intestinal mucosa was alleviated obviously,with remarkable restoration of the continuity of ZO-1. Compared with the sham group,ZO-1 protein levels in the I / R group and the I / R ＋ FICZ group were decreased by 50. 7% and 32. 3%,respectively（ P 〈0. 05）,and compared with the I / R group,ZO-1 protein level in the I / R ＋ FICZ group was increased by 37. 2%（ P 〈0. 05）. Conclusion Pretreatment with FICZ can effectively alleviate the damage of intestinal mucosal structure and function in acute I / R model,and the possible mechanism is to increase the expression of ZO-1.

关 键 词：芳香烃受体 肠黏膜屏障 紧密连接蛋白 肠缺血再灌注 

分 类 号：R333.3[医药卫生—人体生理学] R364.12[医药卫生—基础医学]