白藜芦醇对炎症型肠应激综合征小鼠肠上皮屏障功能的作用  

Effect of Resveratrol on Intestinal Epithelial Barrier Function in Mice with Inflammatory Bowel Stress Syndrome

作　　者：冯杨焜 侯道荣 顾正宇 FENG Yangkun;HOU Daorong;GU Zhengyu(Nantong University,Jiangsu Nantong 226001,China;Nanjing Medical University,Jiangsu Nanjing 211166,China;Nanjing Red Cross Hospital,Jiangsu Nanjing 210001,China)

机构地区：[1]南通大学医学院,江苏南通226001 [2]南京医科大学医药实验动物中心,江苏南京211166 [3]江苏省南京市红十字医院,江苏南京210001

出　　处：《中医药临床杂志》2023年第2期327-333,共7页Clinical Journal of Traditional Chinese Medicine

基　　金：江苏省老年健康科研项目(LX2021001)。

摘　　要：目的:探讨白藜芦醇(resveratrol,RES)对小鼠炎症性肠易激综合征(Post inflammatory irritable bowel syndrome,PI-IBS)作用及其机制。方法:将30只C57BL/6小鼠随机分为正常对照组(Control)、炎症性肠易激综合征模型组(PI-IBS组)和白藜芦醇干预组(PI-IBS+RES)。建立PI-IBS模型,通过粪便含水量和排便次数分别评估小鼠肠粘膜屏障损伤和道通透性变化;内脏敏感性实验来测定大鼠肠道敏感程度;使用免疫组化和Western blot方法测定小鼠海马体和结肠cAMP依赖性蛋白激酶(PKA),磷酸化cAMP反应元件结合蛋白(p-CREB)、脑源性神经营养因子(BDNF)、紧密连接(Tight junction,TJ)蛋白(Occludin、ZO-1、Claudin-2)表达水平。结果:RES对PI-IBS小鼠粪便含水量和粪便颗粒数的增加有明显的抑制作用;改善PI-IBS小鼠肠道高敏状态;显著增加PI-IBS+RES小鼠结肠粘膜中ZO-1和Occludin的表达,下调PKA、p-CREB、BDNF和Claudin-2的表达。此外,RES增加PI-IBS小鼠海马体PKA、p-CREB、BDNF的表达。结论:RES能够改善PI-IBS小鼠肠道通透性和内脏敏感性,调节TJ蛋白的表达,且这一作用与其调节肠道中PKA/CREB/BDNF信号通路蛋白的表达相关。Objective:To investigate the effect and mechanism of Resveratrol(RES)on inflammatory irritable bowel syndrome(Post inflammatory irritable bowel syndrome,PI-IBS)in mice.Methods:Thirty C57BL/6 mice were randomly divided into normal control group(Control),inflammatory bowel syndrome model group(PI-IBS group)and Resveratrol intervention group(PI-IBS+RES).Establish a PI-IBS model,evaluate the intestinal mucosal barrier damage and tract permeability changes in mice through fecal water content and defecation frequency;visceral sensitivity test to determine the degree of intestinal sensitivity in rats;use immunohistochemistry and Western blot methods to determine Mouse hippocampus and colon cAMP-dependent protein kinase(PKA),phosphorylated cAMP response element binding protein(p-CREB),brain-derived neurotrophic factor(BDNF),tight junction(Tight junction,TJ)protein(Occludin,ZO-1,Claudin-2)expression levels.Results:RES significantly inhibited the increase of fecal water content and fecal particle number in PI-IBS mice;improved the intestinal hypersensitivity state of PI-IBS mice;significantly increased ZO-1 in the colonic mucosa of PI IBS+RES mice,Occludin and Claudin-1 expression,down-regulate the expression of PKA,p-CREB,BDNF and Claudin-2.Furthermore,RES increased the expression of PKA,p-CREB,and BDNF in the hippocampus of PI-IBS mice.Conclusion:RES can improve intestinal permeability and visceral sensitivity in PIIBS mice,and regulate the expression of TJ protein,and this effect is related to its regulation of the expression of PKA/CREB/BDNF signaling pathway proteins in the intestine.

关 键 词：白藜芦醇 炎症性肠易激综合征 紧密连接 PKA/CREB/BDNF信号 脑-肠轴 

分 类 号：R271.9[医药卫生—中西医结合]