醛固酮介导心肌成纤维细胞增殖的机制研究

目的探讨醛固酮诱导心肌成纤维细胞(FBs)增殖及对诱导型一氧化氮合成酶一氧化氮(iN-OS-NO)活性的影响。方法以培养的FBs为模型,用醛固酮剌激FBs增殖,螺内酯阻断醛固酮的作用,检测FBsNO含量、iNOS活性和iNOSmRNA表达,用3H-胸腺嘧啶掺入量作为反应FBs增殖的指标。结果醛固酮呈浓度依赖性的促FBs核酸合成速率明显增高,降低FBsNO含量、iNOS活性和iNOSmRNA表达;螺内酯能明显抑制醛固酮介导的FBs核酸合成速率增高,与醛固酮剌激组相比差异显著(P<0.01)。同时发现醛固酮剌激组NO含量、iNOS活性和iNOSmRNA表达与对照组相比差异显著(P<0.05或P<0.01)。螺内酯抑制醛固酮介导的FBs的上述作用。醛固酮干预下FBs核酸合成速率与NO含量及iNOS活性呈显著负相关(r分别为-0.932和-0.928,均P<0.01)。结论醛固酮通过降低iNOS-NO剌激FBs增殖,螺内酯能逆转上述作用。

Study on proliferation mechanism of cardiac fibroblasts mediated by aldosterone

Objective] To investigate the effect of inducible nitric oxide synthase(iNOS)activity in rat cardiac fibroblasts(FBs)under stimulation of aldosterone.Methods] Upon the model of cultured rat FBs,aldosterone was used to stimulated proliferation of FBs,blocked with spironoactone,detecting the NO2-/NO3-contents,iNOS activity and iNOS mRNA expression respectively at different dose with aldosterone,3H-Thymidine(3H-TdR)incorporation as a target to evaluate FBs proliferation.Results] Synthesis rates of nucleic acid of FBs stimulated by aldosterone increased in a dose dependent manner significantly;spironoactone markedly inhibited syntheses of nucleic acid mediated by aldosterone in FBs with a significant difference from aldosterone-stimulated group(P <0.01).Aldosterone(10-11-10-7mol/L)increased FBs NO2-/NO3-contents,iNOs activity and iNOS mRNA expression in a dose dependent manner(P <0.05),the effects of aldosterone were reversed by spironolactone.FBs 3H-TdR incorporation was negatively corrlated with NO2-/NO3-contents and iNOs activity induced by different concentrations of aldosterone(-0.932,-0.928,P <0.01).Conclusion] Aldosterone decreases iNOS-NO system activity in FBs,and stimulates proliferation of FBs.The effect of aldosterone on FBs can be reversed by spironolactone.