Experimental obstructive jaundice alters claudin-4 expression in intestinal mucosa: Effect of bombesin and neurotensin

瞄准：调查试验性的妨碍的黄疸和外长的 bombesin 和 neurotensin (NT )(BBS ) 的影响紧密的连接(TJ ) 的表示上的管理在老鼠的肠上皮的蛋白质 claudin-4。方法：四十只男 Wistar 老鼠随机被划分成五个组：我 = 控制， II = 假冒操作， III = 胆汁管结扎(BDL ) ， IV = BDL+BBS (30 microg/kg 每 d ) ， V = BDL+NT (300 microg/kg 每 d ) 。在 d 的实验的结束 10，内毒素在门和大动脉的血被测量。终端回肠的织物节组织学地被检验并且免疫组织化学地为在肠上皮的 claudin-4 表示的评估。结果：妨碍的黄疸导致了重要的门和大动脉的 endotoxemia 表明的肠的障碍失败。Claudin-4 表示显著地被增加在上面在 jaundiced 老鼠的第三根绒毛并且一起来它的侧面的分发的规定被注意。BBS 或 NT 的管理恢复了 claudin-4 表示到控制状态并且显著地减少了门和大动脉的 endotoxemia。结论：在肠上皮的试验性的妨碍的黄疸增加 claudin-4 表示，它可以是贡献粘膜障碍的混乱的一个关键因素。毁坏规章的肽 BBS， NT 能阻止这扇改变和还原剂门和全身的 endotoxemia。

AIM： To investigate the influence of experimental obstructive jaundice and exogenous bombesin （BBS） and neurotensin （NT） administration on the expression of the tight junction （TJ）-protein claudin-4 in intestinal epithelium of rats. METHODS： Forty male Wistar rats were randomly divided into five groups： Ⅰ = controls, Ⅱ = sham operated,Ⅲ = bile duct ligation （BDL）,Ⅳ = BDL＋BBS （30μg/kg per d）, V = BDL＋NT （300μg/kg per d）. At the end of the experiment on d 10, endotoxin was measured in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically and immunohistochemically for evaluation of claudin-4 expression in intestinal epithelium. RESULTS： Obstructive jaundice led to intestinal barrier failure demonstrated by significant portal and aortic endotoxemia. Claudin-4 expression was significantly increased in the upper third of the villi in jaundiced rats and an upregulation of its lateral distribution was noted. Administration of BBS or NT restored claudin-4 expression to the control state and significantly reduced portal and aortic endotoxemia. CONCLUSION： Experimental obstructive jaundice increases claudin-4 expression in intestinal epithelium,which may be a key factor contributing to the disruption of the mucosal barrier. Gut regulatory peptides BBS and NT can prevent this alteration and reduce portal and systemic endotoxemia.