洛伐他丁对心肌细胞外信号调节激酶信号传导水平及心脏营养素-1表达的影响  

Influence of Lovastatin on Activity Levels of Myocardial Extracellular Signal-Regulated Kinase Signaling Transduction and Expression of Cardiotrophin-1

作　　者：纪红[1] 郭威早[1] 严之红[1] 

机构地区：[1]航天中心医院高干二科,北京100049

出　　处：《中国临床医学》2011年第3期310-313,共4页Chinese Journal of Clinical Medicine

基　　金：航天中心医院科研基金(2009)

摘　　要：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24h和5d,然后以免疫印迹杂交检测p-44ERK1、p-42ERK2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24h后,ERK1、ERK2的磷酸化水平分别升高125%(P=0.041)和89%(P=0.034);处理5d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24h或5d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24h后增高79.3%(P=0.004),处理5d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.

关 键 词：洛伐他丁 细胞外信号调节激酶 甲基戊二酰辅酶A还原酶抑制剂 心脏营养素-1 冠心病 

分 类 号：R972.6[医药卫生—药品]