Hypoxia induced both apoptosis and autophagy,which promote the severity of cardiomyocytes injury.In the present study,we investigated the effect of berberine,a natural extract from Rhizoma coptidis,on the hypoxia-induced autophagy and apoptosis in H9c2 cells.Cellular apoptosis and autophagy levels were found to be upregulated in H9c2 myocytes during hypoxia period,in couple with the reduced cell viability.However,berberine significantly suppressed the hypoxia-induced autophagy (LC3-Ⅱ/LC3-Ⅰ ratio and BNIP3 expression) in H9c2 myocytes and promoted cell survival.Furthermore,Bcl-2 (an anti-apoptosis protein) level was significantly downregulated,and the expression of Bax and cleaved caspase3 (pro-apoptosis protein) was upregulated in cardiac myocytes during hypoxia injury.All these alterations were reversed by berberine treatment and 3-MA (an autophagy inhibitor),while rapamisin (an autophagy agonist) play opposite effect,suggesting berberine decreases cell death through inhibiting autophay to reduce apoptosis in hypoxia-induced myocytes.In addition,Compand C (an AMPK inhibitor) also reduced cell apoptosis and autophagy in hypoxia-induced myocytes,indicating the activation of AMPK pathway involved in the regulation of cell apoptosis and autophagy.Taken together,these findings indicate that the protective effect of berberine against hypoxia-induced apoptosis in H9c2 cells is through inhibiting autophagy levels via suppression of the activation of AMPK.Therefore,berberine may be a promising agent to treat cardiac myocytes injury suffering from ischemia.