Semaglutide Inhibits Ischemia/reperfusion-induced Cardiomyocyte Apoptosis Through Activating PKG/PKCε/ERK1/2 Pathway

Objective:Therefore,this study aimed to test whether semaglutide,a newer GLP-1 analogue,inhibits I/R injury-induced cardiomyocyte apoptosis through activating PKG/PKCε/ERK1/2 pathway.Methods:We induced myocardial I/R injury in the rats and hypoxia/reoxygenation(H/R)injury in the H9C2 cells,and detected the effects of semaglutide,PKG analog(8-Br-c GMP)and PKG inhibitor(KT-5823)on PKG/PKCε/ERK1/2 pathway and cardiomyocyte apoptosis in vivo and in vitro.Results:We found that semaglutide could up-regulate GLP-1R level,and both semaglutide and 8-Br-c GMP could activate PKG/PKCε/ERK1/2 pathway,inhibit myocardial infarction,decrease hs-c TNT level,increase NT-pro BNP level and suppress cardiomyocyte apoptosis in the I/R rats and H/R H9C2 cells.However,KT-5823 exerted opposing effects with semaglutide and 8-Br-c GMP,and KT-5823 could weaken the cardioprotective effects of semaglutide.Conclusion:Semaglutide inhibited I/R injury-induced cardiomyocyte apoptosis through activating PKG/PKCε/ERK1/2 pathway.The beneficial effect of GLP-1/GLP-1R involved in the activation of PKG/PKCε/ERK1/2 pathway might provide novel therapeutic strategies for myocardial I/R injury.