淫羊藿素通过AMPK/NLRP3通路改善脓毒症小鼠心肌损伤的机制研究OA

Objective:To explore the intervention mechanism of icaritin(ICT)on myocardial injury in sepsis.Methods:Mice were divided into control group,model group,AMPK activator(MET)group,icaritin(ICT)group and icaritin+AMPK inhibitor compound C(ICT+CC)group,with 12 mice in each group.Except for the control group,the other mice were intraperitoneally injected with LPS.ICT group was intraperitoneally injected with ICT 30 minutes before modeling,and ICT+CC group was injected with AMPK inhibitor Compound C at the same time.After 24 hours of modeling,cardiac function,myocardial pathological changes,AMPK pathway and pyroptosis-related protein expression,serum inflammatory factors and myocardial injury markers were detected.Results:The intervention of ICT and AMPK activators significantly improved the survival rate of mice,increased cardiac LVEF and LVFS,and decreased LVIDD and LVIDS.Tissue damage was reduced and inflammatory cell infiltration was reduced.The levels of serum TNF-α,IL-1β,IL-18,CK-MB and LDH were decreased.The ratio of p-AMPK/AMPK was increased,and the expression of NLRP3,ASC,Cleaved Caspase-1,GSDMD-NT and Cleaved IL-1β was decreased(P<0.05).Compound C could reverse the improvement effect of ICT on myocardial injury,increase inflammation index and pyroptosis protein expression(P<0.05).Conclusion:ICT can improve myocardial injury and inflammatory response in sepsis mice,and its mechanism may be related to the activation of AMPK to inhibit pyroptosis mediated by NLRP3 signaling pathway.