The Protective Effect Of Bazedoxifene On Intestinal Injury In Sepsis And The Potential Mechanism

Objective: To investigate the effect of BAZ on intestinal injury in sepsis and the relationship with inflammation and pyroptosis.Methods: The sepsis mouse model was established by cecal ligation and perforation(CLP).The effect of BAZ on the 7-day survival rate of CLP mice was analyzed by survival curve.HE staining was used to observe the effect of BAZ on intestinal injury in CLP mice.The m RNA level of inflammatory cytokines in the ileum was detected by q RT-PCR.Immunohistochemical staining was used to detect the expression level of NLRP3 in the ileum.CCK-8 was used to analyze the effect of BAZ on the viability of MODE-K cells induced by LPS and ATP.Western blot was used to detect the level of key molecular markers of pyroptosis,tight junction protein,CD40,and NF-κB signaling.The concentration of LDH in cell culture supernatant was detected by assay Kit.Results: In vivo,the sepsis mouse model was successfully constructed by CLP.BAZ can effectively improve the 7-day survival rate of CLP mice and significantly alleviate CLP induced intestinal injury.BAZ can inhibit intestinal inflammation and pyroptosis caused by CLP.In vitro,LPS and ATP were used to successfully construct the model of cell inflammation and pyroptosis.BAZ can rescue the decrease of cell viability induced by LPS and ATP in a dose-dependent manner.BAZ can inhibit the level of pyroptosis related proteins and the outflow of LDH stimulated by LPS and ATP.In addition,BAZ can inhibit NF-κB signal activation.Conclusion: BAZ can inhibit pyroptosis to reduce intestinal inflammatory injury in sepsis via NF-κB/NLRP3 signaling pathway.The protective effect of BAZ can alleviate the occurrence and development of sepsis.