急性胆道梗阻肠黏膜屏障破坏与氯离子通道-2的关系  

Relationship between CLC-2 and intestinal mucosal barrier in rats with obstructive jaundice

作　　者：陈振勇[1] 王延刚[1] 杨鹏[1] 黄文广[1] 周有生[1] 冯贤松[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院普外科,湖北省武汉市430022

出　　处：《世界华人消化杂志》2011年第27期2829-2834,共6页World Chinese Journal of Digestology

基　　金：湖北省自然科学基金资助项目;No.2010CDB08005~~

摘　　要：目的:探讨急性胆道梗阻肠黏膜屏障破坏与肠上皮细胞氯离子通道-2(chloride channel-2,CLC-2)的关系.方法:建立急性胆道梗阻(阻塞性黄疸)大鼠动物模型,术后7d连续注射Lubiprostone(Lu组)、类高血糖素多肽-2(GLP-2组)、两者共同使用(Lu+GLP组),以假手术组(Sham组)和阻塞性黄疸组(obstructive jaundice,OJ组)作为对照.分别检测实验动物乳果糖/甘露醇(L/M)比值、血浆内毒素水平,并用Westernb l o t s检测末端回肠紧密连接蛋白闭锁小带-1(zonula occludens-1,ZO-1)、CLC-2的表达,并利用图像分析系统对Western blots图像进行定量分析.结果:各实验组的L/M比值均高于Sham组(P=0.00),Lu组(0.545±0.03)、GLP组(0.512±0.03)和Lu+GLP组(0.482±0.05)的数据均低于OJ组(0.656±0.04)(均P=0.00).手术后各组的血浆内毒素均升高,OJ组最高,Lu组、GLP组和Lu+GLP组均有所下降.通过Westernblots研究发现CLC-2蛋白的表达条带出现在90-100KD,ZO-1蛋白条带在200kD左右.定量研究显示OJ组的ZO-1相对表达量(0.178±0.03)明显下降,Lu组(0.209±0.03)高于OJ组而低于Sham组(P=0.02),而Lu+GLP组接近于Sham组.CLC-2蛋白的表达量Sham组为(0.267±0.04),OJ组(0.195±0.04)、GLP-2组(0.217±0.05)和Lu+GLP组(0.222±0.03)均下降明显(均P=0.00).结论:CLC-2和紧密连接蛋白共同参与肠黏膜屏障的维护,急性胆道梗阻破坏肠黏膜屏障与肠上皮细胞的CLC-2有关,促进或激活CLC-2后能活化紧密连接蛋白,修复受损的肠黏膜屏障.AIM： To investigate the relationship between chloride channel-2 （CLC-2） and intestinal mucosal barrier in rats with obstructive jaundice （OJ）. METHODS： Rats were randomly divided into five groups： sham operation group, OJ group, lubiprostone （Lu） group, glucagon-like peptide-2 （GLP-2） group, and Lu ＋ GLP group. Except for the sham operation group, OJ was induced by bile duct ligation in rats of other groups, The Lu group was subcutaneously injected with LU, and the GLP-2 group was injected with GLP-2. The Lu ＋ GLP group was injected with both Lu and GLP-2. The animals were sacrificed 7 days after treatment. The ratio of lactulose to mannitol （L/ M） and plasma endotoxin levels were measured. Western blot was used to examine the changes in the expression tight junction proteins zonula occludens-1 （ZO-1） and CLC-2 in epithelial cells in the terminal ileum. RESULTS： The ratio of L/M was significantly higher in all the experiment groups than in the sham operation group （all P = 0.00）, but was significantly lower in the Lu group, GLP-2 group and Lu ＋ GLP group than in the OJ group （0.545 ± 0.03, 0.512 ± 0.03, 0.482 ± 0.05 vs 0.656 ±0.04, all P = 0.00）. Plasma endotoxin levels increased in all the experiment groups, highest in the OJ group and decreasing somewhat in the Lu group, GLP-2 group and Lu ＋ GLP group. The relative expression of ZO-1 in the Lu group （0.209± 0.03） was higher than that in the OJ group （0.178 ± 0.03） but lower than that in the sham operation group （P =0.02）. The relative expression of ZO-1 in the Lu ＋ GLP group was comparable to that in the sham operation group. The relative expression of CLC-2 descended more obviously in the OJ, GLP-2 and Lu ＋ GLP groups than in the sham operation group （0.195± 0.04, 0.217 ±0.05, 0.222±0.03 vs 0.267 ±0.04, all P = 0.00）. CONCLUSION： CLC-2 and tight junction pro- tein participate in the maintenance of intestinal mucosal barrier. Acute biliary obstruction-induced destruction of intestin

关 键 词：阻塞性黄疸 肠黏膜屏障 紧密连接蛋白 氯离子通道-2 

分 类 号：R333.3[医药卫生—人体生理学]