睾酮对衰老心肌细胞的干预作用及其机制

目的探讨不同剂量睾酮对衰老心肌细胞的干预作用及其可能机制。方法将心肌细胞随机分为正常组、衰老组、1μmol/L睾酮组、100 nmol/L睾酮组、10 nmol/L睾酮组,检测各组心肌细胞周期分布,去磷酸化视网膜母细胞瘤蛋白(RB)表达,细胞内活性氧水平以及细胞线粒体DNA突变率。结果衰老组心肌细胞G_0/G_1期比例较正常组明显升高,而1μmol/L睾酮组、100 nmol/L睾酮组、10 nmol/L睾酮组G_0/G_1期比例较衰老组明显降低(P<0.05)。除10 nmol/L睾酮组对RB表达无明显影响外,睾酮干预可下调去磷酸化RB表达,降低细胞内活性氧水平,降低线粒体DNA突变率(P<0.05,P<0.01)。结论睾酮可抑制小鼠心肌细胞衰老,这一作用部分是通过下调去磷酸化RB表达,降低细胞内活性氧水平,降低线粒体DNA突变率来实现的。

The effects of testosterone on aging cardiac myocytes and the mechanisms

Objective To investigate the effects of testosterone on the aging cardiac myocytes and the possible mechanisms.Methods The cardiomyocytes were randomly divided into five groups: young group,aging group,1μmol/L testosterone group,100 nmol/L testosterone group,10 nmol/ L testosterone group.Then,cell cycle stages,dephosphorylated retinoblastoma(RB) protein,the intracellular reactive oxygen species(ROS) levels and the rate of mitochondrial DNA mutation were measured in each group.Results Compared with the young cardiac myocytes,G_0/G_1 phase of cell cycles in aging cardiac myocytes increased significantly,while in 1μmol/L,100 nmol/L and 10 nmol/L testosterone groups,G_0/G_1 phase of cell cycles decreased as compared with aging group(P<0.05).Except that 10 nmol/L testosterone had no effect on the expression of dephosphorylated RB protein,1μmol/L and 100 nmol/L testosterone could decrease the expression of dephosphorylated RB protein and reduce the ROS levels and the rate of mitochondrial DNA mutation (P<0.05,P<0.01).Conclusion Testosterone can inhibit the senescence of natural aging murine cardiac myocytes,and this effect may be achieved by decreasing the expression of dephosphorylated RB protein,diminishing the ROS levels and the rate of mitochondrial DNA mutation.