中国中医药信息杂志2026，Vol.33Issue(1)：77-83,7.DOI:10.19879/j.cnki.1005-5304.202503749
益糖康调控内质网应激介导NLRP3炎症小体改善db/db小鼠小肠屏障损伤的作用机制研究
Study on Mechanism of Yitangkang in Ameliorating Intestinal Barrier Injury in db/db Mice by Regulating Endoplasmic Reticulum Stress-Mediated NLRP3 Inflammasome Activation
摘要
Abstract
Objective To investigate the mechanism of Yitangkang in ameliorating intestinal barrier injury in db/db mice by regulating endoplasmic reticulum stress(ERS)-mediated NLRP3 inflammasome activation.Methods Totally 30 db/db mice were divided into the model group,Yitakang group and liraglutide group according to random number table method,with 10 mice in each group.Another 10 db/m mice were set as the blank group.After 5 weeks of intervention,fasting blood glucose(FBG),fasting insulin(FINS)and homeostasis model assessment of insulin resistance(HOMA-IR)were measured to assess metabolic status,small intestinal histopathology was evaluated by HE staining,and ultrastructure of small intestinal epithelial cells were observed via electron microscope,the expressions of ZO-1,Occludin,Claudin1 were detected by immunofluorescence,Western blot was used to analyze the related proteins expression of tight junction,ERS,NLRP3 inflammasome and inflammatory cytokine.Results Compared with the blank group,the model group exhibited significantly increased FBG(P<0.01),serum FINS and HOMA-IR(P<0.01);HE staining revealed severe intestinal mucosal damage,inflammatory infiltration and tissue edema in the model group,electron microscope showed widened tight junctions between intestinal epithelial cells;the protein expressions of ZO-1,Occludin and Claudin1 were significantly decreased(P<0.05,P<0.01),while GRP78,CHOP,NLRP3,ASC,cleaved Caspase-1,GSDMD-N,IL-1β and IL-18 significantly increased(P<0.01).Compared with the model group,FBG in liraglutide group significantly decreased after 1 week of administration(P<0.05,P<0.01),FBG in Yitangkang group significantly decreased after 2 weeks of administration(P<0.01),FINS and HOMA-IR in both groups significantly decreased(P<0.01);the results of HE staining showed that the structure of small intestinal mucosa was improved and the inflammatory injury was reduced in Yitangkang group and liraglutide group,the electron microscope results showed that the tight junction structure between the epithelial cells of small intestinal mucosa was dense,and the intercellular space was significantly reduced;the protein expressions of ZO-1,Occludin and Claudin1 in small intestine significantly increased(P<0.05,P<0.01),while the protein expressions of GRP78,CHOP,NLRP3,ASC,cleaved Caspase-1,GSDMD-N,IL-1β and IL-18 significantly decreased(P<0.05,P<0.01).Conclusion Yitangkang may alleviate the activation of NLRP3 inflammasome by inhibiting ERS and improve the intestinal inflammatory response in dB/db mice,so as to repair the damage of diabetic intestinal barrier.关键词
益糖康/2型糖尿病/内质网应激/NOD样受体热蛋白结构域相关蛋白3/小肠屏障损伤Key words
Yitangkang/type 2 diabetes mellitus/endoplasmic reticulum stress/NLRP3/intestinal barrier injury分类
医药卫生引用本文复制引用
王诗怡,孙贵炎,张晖,杨宇峰,石岩..益糖康调控内质网应激介导NLRP3炎症小体改善db/db小鼠小肠屏障损伤的作用机制研究[J].中国中医药信息杂志,2026,33(1):77-83,7.基金项目
国家中医药管理局青年岐黄学者项目(2022年) （2022年）
辽宁省应用基础研究计划(2023JH2/101300050) （2023JH2/101300050）
辽宁省"兴辽英才计划"青年拔尖人才项目(XLYC1807145) （XLYC1807145）
辽宁省科技计划联合计划自然科学基金-博士科研启动项目(2024-BSLH-152) （2024-BSLH-152）
宁波市卫生健康科技计划项目(2024Y66) （2024Y66）
