辛伐他汀改善大鼠心肌梗死后心室重塑与p-ERK1／2的关系  

Simvastatin ameliorates rat ventricular remodeling after myocardial infarction:the role of phosphorylating extracellular signal-regulated kinase1/2

作　　者：胥雪莲[1] 覃数[1] 雷寒[1] 叶强[1] 张茂惠[2] 

机构地区：[1]重庆医科大学附属第一医院心内科,重庆400016 [2]重庆医科大学附属第二医院超声科,重庆400016

出　　处：《中国药理学通报》2008年第2期258-261,共4页Chinese Pharmacological Bulletin

基　　金：重庆自然科学基金资助项目(渝科发计字[2004]54号文)

摘　　要：目的探讨辛伐他汀对大鼠心肌梗死后心室重塑的影响及其与磷酸化细胞外信号调节激酶1／2（p-ERKI／2）的关系。方法结扎Wistar大鼠冠状动脉左前降支建立心肌梗死模型，大鼠随机分为4组（n=8—10）：心肌梗死对照组、辛伐他汀加、40mg处理组和假手术组。4wk后心脏超声检测各组心脏形态和功能，免疫组化法和Western blot检测PERK1／2表达。结果与假手术组相比，心肌梗死对照组及辛伐他汀处理组左室舒张末期内径（LVEDd）、左室后壁厚度（LVPWd）明显增加（P〈0．01），左室射血分数（LVEF）、短轴缩短率（FS）、每博输出量（SV）和心输出量（CO）明显降低（P〈0．01），心肌p-ERK1／2表达明显升高（P〈0．01）。与心肌梗死对照组相比。辛伐他汀处理组LVEDd、LVPWd明显减少（P〈0．01），LVEF、FS、SV和CO明显升高（P〈0．01），心肌p-ERK1／2表达明显下降（P〈0．01）；其中辛伐他汀40mg组比加mg组心肌p-ERK1／2表达下降更明显（P〈0．05）。结论辛伐他汀改善心肌梗死后心室重塑和心功能，其机制可能与下调心肌p-ERK1／2表达有关。Aim To study the effect of simvastatin on ventricular remodeling in rats after myocardial infarction, and the association between this effect and phosphorylating extracellular signal-regulated kinasel/2 （ p- ERK1/2 ）. Methods Myocardial infarction （ MI ） rat models were successfully induced by ligation of anterior descending coronary artery. The treated rats were randomly divided into 4 groups （ n = 8 - 10 ） ： MI only group, MI plus 20 mg Sim group （20 mg ·kg^-1·d^-1）, MI plus 40 mg Sim group（40 mg·kg^-1·d^-1 ）, and sham-operated group. After 4 weeks, the rats were checked by echocardiography including LVEDd, LVPWd, LVEF, FS, SV and CO. Myocardial p- ERK1/2 was also examined by immunohistochemistry and Western blot. Results Compared with sham-oper-ated group, LVEDd, LVPWd in other groups were significantly increased （ P 〈 0. 01 ）, and LVEF, FS, SV and CO were significantly reduced （ P 〈 0. 01 ）. However, simvastatin significantly decreased LVEDd, LVPWd （ P 〈0.01 ）, and increased LVEF, FS, SV and CO （ P 〈 0. 01 ）compared with MI only group. MI significantly increased （ P 〈 0. 01 ） myocardial p-ERK1/2 expres- sion ,while simvastatin dose dependently inhibited myo- cardial p-ERK1/2 expression. Conclusion Simvastatin ameliorated left ventricular remodeling and heart function after MI in rats,which was associated with the effect of decreasing myocardial p-ERK1/2 expression.

关 键 词：辛伐他汀 心肌梗死 心室重塑 细胞外信号调节激酶1/2 

分 类 号：R-332[医药卫生] R322.11