醛固酮与螺内酯对肝星状细胞增殖及胶原合成的影响

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。

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

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 (3)H-thymidine incorporation, and the collagen synthesis by (3)H-Proline. The changes of HSC cycle were analyzed by FCM. RESULTS: At dose of 10(-4) mol/L, ALD increased the incorporation of (3)H-TdR and (3)H-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.