阿托伐他汀对醛固酮诱导心脏成纤维细胞内皮素表达的影响

Effect of atorvastatin on the expression of endothelin induced by aldosterone in cardiac fibroblasts

目的:研究阿托伐他汀对醛固酮诱导大鼠心脏成纤维细胞(CFs)内皮素(ET)表达的影响.方法:以培养的新生SD大鼠CFs为实验模型,放免法检测CFs培养液中ET水平,流式细胞术测定CFs中的ET-1含量,RT-PCR测定内皮素-1前体(ppET-1) mRNA的表达.结果:醛固酮(1×10-7mol/L)组CFs培养液中ET水平和CFs中的ET-1含量及ppET-1 mRNA的表达明显高于正常对照组,差异有统计学意义(P<0.01);醛固酮(1×10-7mol/L)+阿托伐他汀(1×10-6,1×10-5,1×10-4mol/L)组明显低于醛固酮(1×10-7mol/L)组,差异有统计学意义(P<0.01);醛固酮(1×10-7mol/L)+阿托伐他汀(1×10-4mol/L)+甲羟戊酸(1×10-3mol/L)组明显高于醛固酮(1×10-7mol/L)+阿托伐他汀(1×10-4mol/L)组,差异有统计学意义(P<0.01),但和醛固酮(1×10-7mol/L)组接近,差异无统计学意义(P>0.05).结论:阿托伐他汀可抑制醛固酮诱导的CFsppET-1 mRNA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.

AIM： To investigate the effect of atorvastatin on endothelin （ET） expression in cultured rat cardiac fibroblasts （CFs） induced by aldosterone. METHODS： The CFs of neonatal SD rats were isolated and cultured. ET concentration in conditioned medium was measured by radioimmunoassay, intracellular ET-1 level was evaluated by flow cytometry, and the expression of preproendothelin-1 （ ppET-1 ） mRNA was detected and quantified using RT-PCR method. RESULTS： Compared with controls, aldosterone （ 1 × 10^-7 tool/L） group had higher levels of ET concentration in conditioned medium and higher expressions of ppET-1 mRNA and ET-1 in CFs （P 〈0.01 ）. These parameters of aldosterone （ 1 × 10^-7 tool/L） ＋ atorvastatin （ 1 × 10^-6, 10^-5 , 10^-4 moL/L） groups were all significantly lower than those of aldosterone （ 1 × 10^-7 tool/L） group （P 〈0.01 ）. In aldosterone （ 1 × 10^-7 tool/L） ＋ atorvastatin （ 1 × 10^ -4 mol/L） ＋ mevalonate （1 × 10^-3 tooL/L） group, these parameters were all higher than those in aldosterone （ 1 × 10^ -7 moL/L） ＋ atorvastatin （ 1 × 10^-4 tool/L） group （P 〈0.01 ）, however, were similar to those in aldosterone （1 × 10^-7 mol/L） group （P 〉0.05）. CONCLUSION： Atorvastatin can down-regulate ppET-1 mRNA expression, as well as ET-1 synthesis and release induced by aldosterone in a process specifically related to mevalonate in CFs.