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OA

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.