Colchicine alleviates myocardial ischemia-reperfusion injury in mice by activating AMPK

CHEN Guodong; LUO Suxin

doi:10.12122/j.issn.1673-4254.2024.02.04

Abstract：Objective To investigate the protective effect of colchicine against myocardial ischemia-reperfusion injury(I/R)and explore the underlying mechanism.Methods H9C2 cells exposed to hypoxia/reoxygenation(H/R)were treated with 3 nmol/L colchicine,after which the changes in cell viability were assessed using MTT assay,and AMPK phosphorylation,the expressions of NOX4,NRF2,SOD2,BAX,Bcl-2,and cleaved caspase-3 were detected with Western blotting.Male C57BL/6 mice were randomized into sham operation,I/R,I/R+colchicine,and I/R+colchicine+dorsomorphin(DSMP)groups.After the treatments,myocardial expressions of p-AMPK/AMPK,8-OHdG,cleaved caspase-3,mitochondrial BAX(Mito-BAX),and cytoplasmic cytochrome C(Cyt-Cyto C)were examined and cardiac functions,infarct area,ATP content,and serum levels of lactic dehydrogenase(LDH)and cardiac troponin T(cTnT)levels were assessed.Results In H9C2 cells,H/R exposure significantly reduced AMPK phosphorylation and expressions of NRF2,SOD2,and Bcl-2,lowered cell viability,and up-regulated the expressions of NOX4,BAX,and cleaved caspase-3(P<0.05),and these changes were obviously alleviated by colchicine treatment(P<0.05).In the mouse models,myocardial I/R injury significantly reduced myocardial AMPK phosphorylation level,ATP content,and expressions of NRF2,SOD2 and Bcl-2,caused cardiac function impairment,enhanced NOX4,Mito-BAX,Cyt-Cyto C,BAX,8-OHdG,and cleaved caspase-3 expressions,and increased infarct area and serum LDH and cTnT levels(P<0.05).Colchicine treatment significantly reversed the damaging effects of I/R(P<0.05),but its protective effects was obviously antagonized by DSMP(P<0.05).Conclusion Colchicine alleviates myocardial I/R injury and protects cardiac function in mice by reducing myocardial oxidative stress and apoptosis via activating AMPK.