目的:探讨细胞外信号调节激酶(ERK)通路与甲基戊二酰辅酶A (HGM-CoA)还原酶抑制剂的关系.方法:体外培养的大鼠心肌细胞株H9c2(2-1)经洛伐他丁处理24 h和5 d,然后以免疫印迹杂交检测 p-44 ERK1、p-42 ERK2和总ERK蛋白水平,同时检测心脏营养素-1蛋白水平的变化.结果:洛伐他丁处理24 h后,ERK1、ERK2的磷酸化水平分别升高125%(P=0.041)和89%(P=0.034);处理5 d后检测ERK1、ERK2的磷酸化水平分别升高93%(P=0.021)和80%(P=0.046).培养中的大鼠心肌细胞H9c2(2-1)经过洛伐他丁处理24 h或5 d后,作为重要炎性细胞因子的心脏营养素-1水平均显著增高,其中,处理24 h后增高79.3%(P=0.004),处理5 d后增高34.8%(P=0.014).选择性抑制ERK之后,洛伐他丁处理导致心脏营养素-1水平的变化显著减弱.结论:洛伐他丁除了具有已知的降脂作用外,亦可能参与心肌细胞炎性反应的调节机制.%Objective: To investigate the relationship between extracellular signal-regulated kinase (ERK) signaling pathway and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor. Methods: Rat myocardial H9c2 (2-1) cells in culture were subjected to lovastatin treatment for 24d and 5d, protein levels of p-44 ERK1 and p-42 ERK2 as well as cardiotrophin-1 were analyzed with immunnoblotting. Results: After 24h treatment of lovastatin, the phosphorylation levels of ERK1 and ERK2 were increased by 125％ (P = 0.041) and 89％ (P = 0.034) respectively, when the treatment was extended to 5d,the phosphorylation levels of ERK1 and ERK2 were increased by 93％ (P = 0. 021) and 80％ (P = 0. 044) respectively. Meanwhile, as an important inflammatory cytokine, the protein levels of cardiotrophin-1 were up-regulated by 79. 3％ (P = 0. 004) after 24h and 34.8％ (P = 0. 014) after 5d treatments of lovastatin. After application of selective ERK inhibitor, the changes of cardiotrophin-1 levels after lovastatin were largely attenuated. Conclusions: Besides the generally recognized lowering-cholesterol role, it is likely that lovastatin also get involved in the regulation of inflammation reaction of myocardium.
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