睾酮诱导大鼠心肌细胞肥大反应并上调ERK1/2蛋白表达  

Testosterone induces cardiomyocyte hypertrophy in rats and upregulates the expression of ERK1/2

作　　者：王庭槐[1] 许研 刘海梅[1] 崔雨虹[1] 徐进文[1] 蒋萍[1] 付晓东[1] 

机构地区：[1]中山大学中山医学院生理学教研室,广东广州510080 [2]广州市第十一人民医院,广东广州510530

出　　处：《基础医学与临床》2010年第5期449-453,共5页Basic and Clinical Medicine

基　　金：国家自然科学基金(30250010)

摘　　要：目的探讨细胞外信号调节激酶(ERK1/2蛋白)在睾酮对大鼠心肌肥大中的作用。方法用差速贴壁法分离及纯化培养新生SD大鼠心肌细胞,以Bradford法测定心肌细胞蛋白质含量,同位素法分析3H-亮氨酸(3H-Leu)掺入,IBAS图像分析心肌细胞表面积,以免疫印迹法检测心肌细胞ERK1/2蛋白表达水平。结果生理浓度的T作用于大鼠心肌细胞24 h后,细胞蛋白质含量3、H-Leu掺入和细胞表面积均增加,其中以10-8mol/L作用最强。雄激素受体拮抗剂氟他胺(Flu)10-5mol/L预处理2 h可抑制T诱导的心肌细胞蛋白质含量的增加,而Flu单独作用对心肌细胞蛋白质含量无影响。ERK1/2信号通路的特异性抑制剂PD98059 50μmol/L预处理2 h,可抑制T诱导的心肌细胞3H-Leu掺入的增加;10-8mol/L T作用24 h使心肌细胞的ERK1/2的蛋白表达显著增加;10-5mol/L Flu预处理2 h可逆转T诱导的心肌细胞ERK1/2蛋白表达的增加。结论生理浓度的T可以诱导心肌细胞肥大反应,该作用可能由ERK1/2信号通路介导。T通过雄激素受体(AR)上调ERK1/2蛋白表达。Objective To explore the role of ERK1/2 protein in development of myocardial hypertrophy.MethodsMyocardial cells were isolated from ventricles of 1～3-day-old neonate rats and purifed by a culture method.Neonate rat cardiomyocyte hypertrophic responses were assayed by measuring protein content,protein synthesis rate and cell surface area.Expression of protein ERK1/2 were detected by Western blot.Results Cell protein content,3H-leucine（3H-Leu） incorporation and cell surface area increased by treating of cardiomyocytes with T（10^-10～10^-6mol/L） for 24 h.The maxium effect was observed at the concentration of 10^8mol/L.The increase of cell protein content induced by T was inhibited by pretreating with flutamide（10^-5mol/L） for 2 h,while there was no effect on cardiomyocytes pretreating with flutamide alone.The increase of 3H-Leu incorporation induced by T was blocked by PD98059（50 μmol/L）.Expression of ERK1/2 was upregulated significantly by treating with testosterone for 24 h at the level of 10^-8mol/L.The increased expression of ERK1/2 induced by T was reversed by pre-treating with flutamide（10-5mol/L） for 2 h.Conclusion T with physio-concentration may induce cardiomyocyte hypertrophy and this effect was possibly mediated through the activation of ERK1/2 signalling.During this procession,T upregulated the protein expression of ERK1/2 mediated by androgen receptor.

关 键 词：睾酮 心肌细胞肥大 细胞外信号调节激酶1/2 信号传导 

分 类 号：R541[医药卫生—心血管疾病]