替普瑞酮对急性胰腺炎大鼠肠黏膜屏障保护作用的实验研究  

Protective Effect of Teprenone on Intestinal Mucosal Barrier in Rats with Experimental Acute Pancreatitis

作　　者：郭晓榕[1] 刘晓[1] 李洁[1] 吴敏[1] 湛先保[1] 

机构地区：[1]第二军医大学长海医院消化内科,200433

出　　处：《胃肠病学》2015年第10期602-605,共4页Chinese Journal of Gastroenterology

基　　金：国家自然科学基金(81500485)

摘　　要：背景:肠黏膜屏障功能损害是急性胰腺炎(AP)发生、发展的关键环节,与疾病预后密切相关。目的:探讨黏膜保护剂替普瑞酮对AP大鼠模型肠黏膜屏障的保护作用及其可能机制。方法:45只成年雄性Sprague-Dawley大鼠随机分为正常对照组(n=5)、AP模型组(n=20)和替普瑞酮治疗组(n=20)。造模大鼠腹部皮下注射雨蛙素,治疗组造模前后予替普瑞酮灌胃。以ELISA法检测血清白细胞介素-1(IL-1)、IL-6、肿瘤坏死因子-α(TNF-α)和淀粉酶水平,分别以光学显微镜和透射电子显微镜观察小肠黏膜组织病理学和超微结构变化,蛋白质印迹法检测紧密连接蛋白occludin、ZO-1表达。结果:AP模型组血清IL-1、IL-6、TNF-α和淀粉酶水平较正常对照组显著升高(P<0.05),小肠黏膜绒毛坏死脱落,上皮细胞间紧密连接明显增宽,occludin、ZO-1蛋白表达下调;替普瑞酮治疗组血清促炎细胞因子和淀粉酶水平较AP模型组显著降低(P<0.05),小肠绒毛仍较完整,紧密连接致密,occludin、ZO-1蛋白表达增强。结论:在AP大鼠模型中,替普瑞酮可能通过上调紧密连接蛋白表达对肠黏膜屏障发挥保护作用。Background：Damage of intestinal mucosal barrier is a key factor in the development and progress of acute pancreatitis（AP）,and is closely related with the prognosis of the disease. Aims：To investigate the protective effect and possible mechanism of mucoprotective agent teprenone on intestinal mucosal barrier in rats with experimental AP. Methods：Forty-five adult male Sprague-Dawley rats were randomly divided into normal control group（n = 5）,AP model group（n = 20）and teprenone treated group（n = 20）. AP model was established by subcutaneous injection of cerulein at abdominal wall. Rats in treated group were intervened with teprenone intragastrically before and after model establishment. ELISA was used for measurement of serum interleukin-1（IL-1）,IL-6,tumor necrosis factor-α（TNF-α）and amylase;histopathological and ultrastructural changes of small intestinal mucosa were observed by light microscope and transmission electron microscope;Western blotting was used to detect the expressions of tight junction protein occludin and ZO-1. Results：Serum levels of IL-1,IL-6,TNF-α and amylase in AP model group were significantly higher than those in normal control group（P〈 0. 05）,accompanied by necrosis and exfoliation of small intestinal villus,widening of intercellular tight junctions and downregulation of occludin and ZO-1 expression. While in teprenone treated group,serum levels of proinflammatory cytokines and amylase were significantly decreased as compared with AP model group（P〈 0. 05）,the villus of small intestine remained intact,and dense tight junctions were observed. Expressions of occludin and ZO-1 in teprenone treated group were upregulated. Conclusions：Teprenone may protect against intestinal mucosal barrier injury in AP model rats by upregulating tight junction protein expression.

关 键 词：急性胰腺炎 替普瑞酮 肠黏膜屏障 紧密连接 OCCLUDIN ZO-1 

分 类 号：R576[医药卫生—消化系统]