醛固酮对新生大鼠心肌成纤维细胞分泌ET、NO和TGF-β_1功能的影响

Effects of Aldosterone on the production of ET, NO and TGF-β_1 in m yocardial fibroblasts in neonatal rat

目的 探讨醛固酮对新生大鼠心肌成纤维细胞 (CFs)分泌内皮素 (ET)、一氧化氮 (NO)和转化生长因子 β1(TGF β1)的影响。方法 采用胰酶消化法和差速贴壁分离法获取CFs,应用放射免疫分析法、硝酸还原酶法和ELISA法分别测定不同条件下培养的CFs培养液中的ET、NO和TGF β1水平。结果 一定浓度范围内的醛固酮可按剂量依赖方式促进CFs分泌ET和TGF β1,抑制CFs分泌NO ,使ET/NO比值上升 ;盐皮质激素受体 (MR)拮抗剂螺内酯可阻断醛固酮的上述作用 (P <0 0 1)。结论 醛固酮可通过MR促新生大鼠CFs分泌ET和TGF β1,抑制CFs分泌NO ,从而改变ET/NO比值。醛固酮可能通过影响CFs分泌的生物活性物质网络平衡关系改变 ,发挥其促心肌纤维化作用。

Objective To investigate the effects of aldosterone on the production of ET, NO and TGF-β 1 in cardiac fibroblasts(CFs) in neon atal rat. Methods CFs were isolated by trypsin digestion method, the changes of ET, NO and TGF-β 1 production from CFs were examined by ra dioimmunoassay, nitrate reductase-dependent assay and by ELISA, respectively. Results Aldosterone (1×10\+\{-10\}-1×10\+\{-7\} mol/L) incr eased ET and TGF-β 1 synthesis and decreased NO synthesis in CFs in a con centration-dependent manner (P<005), which was blocked by sp ironolactone. Conclusion These results showed that aldosteron e increase the production of ET, TGF-β 1 and decrease the production of NO in neonatal rat CFs via mineralocorticoid receptor. Aldosterone may induce myo cardial fibrosis by modulating these complicated balances between vasoactive fac tors produced from CFs.