醛固酮对心脏成纤维细胞转化生长因子β_1的影响

Effects of Aldosterone on the expression of transforming growth factor-beta 1 in cardiac fibroblasts

目的探讨醛固酮对心脏成纤维细胞转化生长因子β(1TGF-β1)的影响。方法采用胰酶消化法和差速贴壁分离法获取新生大鼠心脏成纤维细胞,应用ELISA、Western-Blot、RT-PCR的方法分别测定不同条件下心脏成纤维细胞培养液中TGF-β1水平和心脏成纤维细胞中的TGF-β1含量,以及TGF-β1mRNA的表达。结果醛固酮(10-9、10-8和10-7mol/L)可剂量依赖性地促进心脏成纤维细胞TGF-β1mRNA的表达以及TGF-β1的合成和分泌,同时醛固酮(10-7mol/L)以时间依赖的方式促进TGF-β1mRNA的表达,在作用4h后表达开始增加,8h达高峰。提前给予螺内酯(10-6mol/L)能抑制醛固酮(10-7mol/L)的上述作用。结论醛固酮能促使心脏成纤维细胞TGF-β1mRNA的表达以及TGF-β1的合成和分泌,且此作用可能是通过盐皮质激素受体介导的。

[ Objective ] To investigate the effects of Aldosterone on the expression of transforming growth factor-beta 1 （TGF-β1） in cardiac fibroblasts. [Methods] Neonatal rat cardiac fibroblasts were isolated by trypsin digestion and different speed adherence methods. TGF-β1 concentration of culture solution, intracellular TGF-β1 level, and TGF-β1 mRNA expression in different condition were measured by ELISA, Western-Blot, and RT-PCR methods, respectively. [Results] Aldosterone （10^-9, 10^-8, 10^-7 mol/L） induced a dose-dependent changes in TGF-β1 mRNA expression, as well as TGF-β1 synthesis and secretion in cardiac fibroblasts. Meanwhile, aldosterone （10^-7 mol/L） timerelated induced TGF-β1 mRNA expression in cardiac fibroblasts, which began to increase in 4 h and attained the highest level in 8 h. The effects of Aldosterone （10^-7 tool/L） were significantly inhibited by the pre-incubation with Spironolaetone （10^-6 mol/L）. [ Conclusion ] These results showed that Aldosterone increased the expression of TGF-β1 mRNA, as well as TGF-β1 synthesis and secretion via mineralocorticoid receptor in cardiac fibroblasts.