醛固酮与螺内酯对肝星状细胞增殖及胶原合成的影响

Effects of aldosterone and spironolactone on the proliferation and collagen synthesis of hepatic stellate cells in rats

目的 探讨醛固酮 (ALD)、螺内酯对大鼠肝星状细胞 (HSC)增殖、胶原合成的影响。方法 大鼠HSC培养 ,在不同浓度的ALD、螺内酯作用下 ,采用3 H 胸腺嘧啶核苷 (3 H TdR)、3 H 脯氨酸 (3 H Pro)掺入法及流式细胞技术观察ALD、螺内酯对HSC增殖及胶原合成的影响。结果 ALD在 10 -4mol/L高浓度时3 H TdR、3 H Pro掺入量与对照组相比明显增多 (P <0 .0 5 ) ,螺内酯在浓度高于 10 -6mol/L时 ,HSC3 H TdR、3 H Pro掺入量明显减少 ,螺内酯阻止HSC于G1期 ,ALD +螺内酯组与对照组相比差异无显著意义 (P >0 .0 5 )。结论 高浓度ALD可以促使HSC增殖 ,其拮抗剂螺内酯明显抑制HSC的增殖及合成胶原。

Objective To investigate the effects of aldosterone and spironolactone on the proliferation and collagen synthesis of hepatic stellate cells. Methods Rat HSC were incubated with aldosterone or spironolactone,an aldosterone receptor antagonist at different concentrations. The proliferation of HSC was measured by 3H-thymidine incorporation,and the collagen synthesis by 3H-Proline. The changes of HSC cycle were analyzed by FCM. Results At dose of 10 -4 mol/L,ALD increased the incorporation of 3H-TdR and 3H-Pro( P <0.05),but didn′t at the lower doses. Spironolactone significantly inhibited HSC proliferation and collagen synthesis. The effective concentration was among 10 -4 mol/L～10 -6 mol/L,and in dose-dependent manner. The percentage of G_1 phase of the cell cycle was significantly increased,and the cell proliferation suppression of spironolactone is associated with cell arrest in G_1 phase. Co-stimulation with aldosterone and spironolactone did not have significant effects on HSC proliferation and collagen synthesis compared with the control group. Conclusion The proliferation and collagen synthesis of HSC might be enhanced by ALD at higher concentration, but was inhibited by spironolactone.