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目的:探讨普伐他汀对醛固酮诱导新生大鼠心脏成纤维细胞内皮素(ET)的影响。方法:采用胰酶消化法和差速贴壁分离法获取和培养新生大鼠心脏成纤维细胞,应用放免法、流式细胞术、RT-PCR的方法分别测定醛固酮、普伐他汀以及甲羟戊酸干预下心脏成纤维细胞培养液中ET水平和心脏成纤维细胞中的ET-1含量,以及内皮素-1前体(ppET-1)mRNA的表达。结果:与正常对照组相比,醛固酮(10-7mol/L)可促进心脏成纤维细胞培养液中ET水平和心脏成纤维细胞中的ET-1含量及ppET-1 mRNA的表达,提前给予普伐他汀(10-5,10-4,10-3mol/L)能剂量依赖性地抑制醛固酮的上述作用,同时这种抑制作用可被甲羟戊酸所逆转。结论:普伐他汀可抑制醛固酮诱导的心脏成纤维细胞ppET-1mRNA表达以及ET-1的合成和分泌,其机制可能与甲羟戊酸代谢途径有关。
Objective: To investigate the effect of pravastatin on aldosterone induced endothelin (ET) in neonatal rat cardiac fibroblasts. METHODS: Newborn rat cardiac fibroblasts were isolated and cultured by trypsin digestion and differential adherent separation. The levels of aldosterone, pravastatin and methionine were determined by radioimmunoassay, flow cytometry and RT-PCR respectively. The level of ET in cardiac fibroblast culture medium and the content of ET-1 in cardiac fibroblasts, and the expression of endothelin-1 precursor (ppET-1) mRNA in the acid intervention group. Results: Compared with the normal control group, aldosterone (10-7mol / L) could promote ET level in cardiac fibroblast culture medium and the content of ET-1 in cardiac fibroblasts and the expression of ppET-1 mRNA, Statin (10-5, 10-4, 10-3mol / L) dose-dependently inhibited the above effects of aldosterone, and this inhibition could be reversed by mevalonate. Conclusion: Pravastatin can inhibit aldosterone-induced cardiac fibroblasts ppET-1mRNA expression and ET-1 synthesis and secretion, the mechanism may be related to mevalonate metabolic pathway.