实验性梗阻性黄疸小肠黏膜上皮紧密连接蛋白的改变  

The alteration of intestinal mucosal tight junction proteins in experimental obstructive jaundice

作　　者：陈振勇[1] 冯贤松[1] 周有生[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,武汉市430022

出　　处：《实用医学杂志》2008年第22期3845-3847,共3页The Journal of Practical Medicine

摘　　要：目的:寻求梗阻性黄疸肠黏膜屏障破坏的机制。方法:建立大鼠梗阻性黄疸模型,于胆总管结扎10d后,采用免疫组化和Western blots免疫印迹检测末端回肠黏膜紧密连接蛋白ZO-1(zonula occludens-1),闭锁蛋白(occludin),壳牢素-1,4(claudin-1,-4)的分布和表达,并利用图像分析系统对Western blots图像结果进行定量分析。结果:梗阻性黄疸时大鼠回肠黏膜萎缩明显,平均肠绒毛高度、黏膜厚度和隐窝深度与对照组比较分别下降27.8%、21.7%和25.4%(均P<0.01)。正常回肠黏膜ZO-1、闭锁蛋白及壳牢素-1分布相似,主要位于顶端细胞膜,沿绒毛下方、均匀连续分布;梗阻性黄疸时分布散乱异常,染色变浅;强阳性表达率分别从对照组的70.0%、80.0%和90.0%降至实验组的35.7%、32.1%和39.2%(均P<0.05),且肠绒毛高度的下降与ZO-1表达率的降低成正相关(P<0.01)。而壳牢素-4的数量和分布改变不明显。对Westernblot图像定量分析得到相同的结果。结论:梗阻性黄疸时小肠黏膜上皮紧密连接蛋白分布异常及数量改变,影响肠黏膜上皮屏障的完整性,破坏小肠黏膜屏障。Objective To explore the mechanism Of intestinal mucosal barrier impairment in obstructive jaundice. Methods A murine model of obstructive jaundice was established. 10 days after establishment, the distribution and expressions of tight junction proteins ZO-1, occludin, and claudin-1 ,-4 were detected by immunohistochemistry and Western blot in the terminal ileum mucosa. Results The ileum mucosa shrank evidently in the experimental rats. As compared with the controls, the average villus height, mucosal thickness, and crypt depth were decreased by 27.8%, 21.7%, and 25.4%, respectively （P 〈 0.01 for all comparisons）. ZO-1, occludin, and claudin-1 were similar in distribution in the normal mucosa, mainly localizing at the apical membrane and distributing evenly along the inferior part of the villus, but were abnormally distributed in the rats with obstructive jaundice, with vague staining. The strong positive rates of ZO-1, occludin, and claudin-I were declined from 70.0%, 80.0%, and 90.0% in the control group to 35.7%, 32.1%, and 39.2% in the experiment group （P 〈 0.05 for all comparisons）. The decrease in villus height was positively related with the decline in ZO-1 expression （P 〈 0.01 ）. No marked changes in the distribution and quantity of claudin-4 occurred. Conclusion Obstructive jaundice induces the abnormal distribution of tight junction proteins and the alteration of their quantity, which affects the intestinal barrier integrity, resulting in impaired barrier function.

关 键 词：黄疸 阻塞性 紧密连接蛋白 肠黏膜屏障 

分 类 号：R657.4[医药卫生—外科学]