Carvedilol antagonizes hypoxia/reoxygenation-induced apoptosis in cultured neonatal rat cardiomyocytes

Objective To observe the effects of carvedilol against hypoxia/reoxygenation-induced apopto- sis in cultured neonatal rat cardiomyocytes and explore its possible mechanism.Methods The cardiomyocytes isolated and purified from neonatal SD rats(1 to 3 days old)were cultured for 72 h and divided into the control group,hypoxia/reoxygenation group,and carvedilol-pretreated hypoxia/reoxygenation group.Hypoxia/reoxy- genation model was established by exposing the cardiomyocytes to anoxia for 120 min followed by reoxygenation for 30 min.The protective effect of carvedilol on cardiomyocyte survival after hypoxia/reoxygenation exposure was evaluated,and its effect on Bcl-2 and Bax expression in the cardiomyoctyes was assessed using immunohis- tochemistry.Results The viable cell percentage in the carvedilol-pretreated hypoxia/reoxygenation group was (70.21±2.12)%,significantly higher than that of(58.39±3.22)% in the hypoxia/reoxygenation group.Im- munohistochemistry demonstrated no significant difference in Bcl-2 expression between the carvedilol-pretreated group and the hypoxia/reoxygenation group([12.22±1.62]% vs[20.32±3.62]%,P0.05),but the carve- dilol-pretreated cells showed significantly lowered Bax expression[(32.62±4.22)% vs(40.21±3.22)%,P0.05],resulting in significant difference in the Bcl-2/Bax ratio between the two groups(0.62 vs O.30,P0.05).Conclusion Carvedilol can significantly reduce cardiomyocyte apoptosis in response to hypoxia/reoxy- genation exposure,possibly by inhibiting Bax expression to increase of Bcl-2/Bax ratio in the cardiomyocytes. (Shanghai Med J,2008,31:184-186)