丝裂原活化蛋白激酶在醛固酮诱导心室成纤维细胞增殖中的作用

MAPK signal transduction mechanisms in the inductive effects on cardiac fibroblasts proliferation in neonatal rat induced by aldosterone

目的:探讨醛固酮诱导心肌成纤维细胞(CFs)增殖的信号转导机制。方法:用胰酶消化法分离、培养新生大鼠CFs,采用3H-胸腺嘧啶核苷(3H-TdR)掺入法、western-blotting技术从DNA合成、蛋白表达等方面观察MAPK活化与醛固酮促CFs增殖的关系。结果:①醛固酮剂量依赖性促CFsDNA合成,10-5mol/LPD98059[(782±152)个·min-1]可逆转10-7mol/L醛固酮[(1879±169)个·min-1]的作用;②10-7mol/L醛固酮对活化MAPK蛋白表达有显著增强作用,在4h达峰作用(8.11±0.46),10-7mol/L醛固酮的作用(8.11±0.46)被10-5mol/LPD98059(1.21±0.10,P<0.01)阻断。结论:醛固酮能激活CFs的MAPK,MAPK表达及活化参与醛固酮诱导的CFs增殖。

Objective： To provide experimental evidence for Ras-MAPK signal regulating cardiac fibroblasts proliferation induced by aldosterone. Method.. The DNA synthesis of cardiac fibroblasts was determined by 3 H- Thymidine （3 H-TdR） incorporation. Western blotting analysis detected phosphorylated MAPK protein expression. Result：（DAldosterone promoted the proliferation of cardiac fibroblasts in a dose dependent manner, PD98059 in concentration of 10^-7mol/L [（782±152）counts · min^-1] reversed the effects of 10^-7mol/L aldosterone [（1879± 169） counts · min^-1]. （2）10^-7 mol/L aldosterone significantly increased the levels of the activated （phosphorylated）MAPK protein, and the levels of peak of activity of phospho- MAPK （8. 11 ±0. 46 fold at 4 hours）. Aldosterone with a concentration of 10^-7 mol/L significantly increased the phosphorylated MAPK protein levels at 4 hours （8.11 ±0.46）, while PD98059 in a concentration of 10 5 mol/L significantly decreased the phosphorylated MAPK protein levels （1.21± 0. 10, P〈0.01）. Conclusion： Aldosterone could stimulate MAPK activity, which led to cell proliferation.