Regulatory effect mechanism of Shenling Baizhu Powder on canonical pyroptosis pathway and intestinal tight junction in mice with chronic ulcerative colitis
Objective:To explore the regulatory effect and mechanism of Shenling Baizhu Powder(SLBZS)on canonical pyroptosis pathway and intestinal tight junction in mice with chronic ulcerative colitis(UC).Methods:Thirty-two C57BL/6 mice were randomly divided into control group,model group,SLBZS group and 5-ASA group.The mice were administered 2.5%dextran sulfate sodium salt(DSS)in daily drinking to induce chronic UC,and were given the corresponding drugs by intragastric administration from the 15th day.The general condition,body weight,stool characteristics and stool blood of mice were observed,and the DAI score was calculated.The histopathological changes of colon were observed by HE staining.The contents of inflammatory cytokines IL-1β and IL-18 in colon tissue were detected by ELISA.The protein expression of tight junction ZO-1,Occludin,and the cell pyroptosis NLRP3,GSDMD-N and c-caspase-1 in colon tissue were detected by Western Blot.Results:Compared with the control group,colon length of the model group was significantly shortened(P<0.01),DAI score was increased,inflammatory cells were infiltrated in colon tissue,and the mucosal layer was necrotic and exfoliated seriously,the histopathological score was significantly increased(P<0.01),the contents of inflammatory cytokines IL-1β and IL-18 in colon tissue were significantly increased(P<0.01),the protein expression of ZO-1 and Occludin were significantly decreased(P<0.01),the protein expression of NLRP,GSDMD-N and c-caspase-1 were significantly increased(P<0.01).Compared with the model group,colon length of SLBZS group was lengthened(P<0.05),DAI score was decreased,the histopathological score was decreased(P<0.05),the contents of inflammatory cytokines IL-1 β and IL-18 were significantly decreased(P<0.01),the protein expression of ZO-1 and Occludin were significantly increased(P<0.01),the protein expression of NLRP3,GSDMD-N and c-caspase-1 were significantly decreased(P<0.01).Compared with 5-ASA group,the protein expression of NLRP3 and c-caspase-1 in colon tissue of SLBZS group were significantly decreased(P<0.01,P<0.05),the protein expression of Occludin was significantly increased(P<0.01).Conclusion:SLBZS has the effect of preventing and treating chronic UC,and its mechanism is related to the regulation of colon tissue canonical pyroptosis pathway and intestinal tight junction,and reduction of inflammatory factors expression.