低氧及低氧预处理时心肌细胞HIF-1α与凋亡相关蛋白表达的变化

CHANGES IN EXPRESSION OF APOPTOSIS CORRELATIVE PROTEINS AND HIF-1 DURING ACUTE HYPOXIA AND HYPOXIC PRECONDITIONING IN CULTURED CARDIOMYOCYTE OF RAT

目的:观察低氧时心肌细胞HIF-1α表达变化与凋亡相关蛋白表达关系.方法:采用体外心肌细胞培养的方法,将原代培养4～6 d的大鼠乳鼠心肌细胞随机分为对照组、低氧组与低氧预处理组.低氧预处理组在低氧培养箱中通入1%O2、5%CO2、94%N2的低氧混合气体,每天低氧12 h,低氧5 d,第6 d与急性低氧组一同放入0%O2、5%CO2、95%N2的低氧培养箱中进行低氧暴露.低氧48 h后,通过Western blot方法分别检测心肌细胞中HIF-1α、Bcl-2、P53及Bax的表达变化.结果:常氧时细胞不表达HIF-1α,低氧可增加HIF-1的表达,低氧预处理后,能降低HIF-1α的表达.低氧时,Bax的表达变化大致与此相同.p53在低氧时的变化也与其相同,但低氧预处理后似乎没有明显的改变.Bcl-2在低氧时表达下降,低氧预处理后可增加其表达.结论:HIF-1α的表达可协同Bcl-2家族凋亡相关蛋白的表达,在低氧导致的心肌细胞凋亡中发挥重要作用.

Aim： To investigate the relationship between the hypoxia-inducible factor 1 （HIF-1 ） and apoptosis correlative proteins in the cardiomycyte during hypoxia. Methods： Rat cardiomyocytes cultured in vitro were divided into normoxia, hypoxia and hypoxie preconditioning groups. The eardiomyocytes in hypoxic preconditioning group were cultured in 1% O2 ,5 % CO2,94 % N2 for 5 days, 12 h daily before exposed to 0% O2 hypoxia with the hypoxic group. The protein expression of HIF-1α, Bcl-2, P53 and Bax in the cardiomyocytes were analysis with Western blot after 48 h 0% O2 hypoxia. Results： With the increment of HIF-1 expression, the Bcl- 2 expression was inhibited, the Bax and P53 expression were increased as well during hypoxia. Hypoxic preconditioning could sup- press the HIF-1 expression, meanwhile the Bcl-2 expression was elevated, and the Bax expression was decreased. Conclusion： HIF- 1 may contribute to the regulation of the cardiomyocyte apoptosis with the Bcl-2 family during hypoxia.