辛伐他汀干预急性心肌梗死后心肌营养素-1的表达与左室重塑的关系  

Simvastatin therapy on CT-1 after AMI and its relativity with ventricular remolding

作　　者：杨义[1] 覃数[1] 刘俊[1] 郎清[1] 何泉[1] 

机构地区：[1]重庆医科大学附属第一医院心内科,重庆400016

出　　处：《中国药理学通报》2009年第3期386-390,共5页Chinese Pharmacological Bulletin

基　　金：重庆市自然科学基金资助项目[No渝发科技字(2004)54号文]

摘　　要：目的研究辛伐他汀干预急性心肌梗死(AMI)后左室非梗死区(LVNIZ)心肌营养素-1(CT-1)表达及左室重塑(LVRM)的进程。方法♂SD大鼠分为4组,AMI组、AMI+辛伐他汀组、假手术组和正常组,每组8只。前2组大鼠结扎左冠状动脉前降支(LAD)制备成AMI模型。AMI+辛伐他汀组在手术后d2予辛伐他汀40mg.kg-1.d-1灌胃。余3组给予生理盐水灌胃。4wk后测定左室重量指数,LVNIZ心肌细胞横截面积,LVNIZ心肌胶原容积分数变化,用RT-PCR和Western blot法测定LVNIZ CT-1mRNA表达和蛋白合成水平。结果与正常和假手术组比较,AMI组LVRM参数:左室重量指数(LVWI),心肌细胞横截面积(CA),Ⅰ、Ⅲ胶原容积分数(CVFⅠ、CVFⅢ),均明显增加(P<0.05),LVNIZ CT-1mRNA表达和蛋白合成水平于4wk后明显增加(P<0.05)。与AMI组相比,AMI+辛伐他汀组LVRM明显减轻,LVNIZ CT-1mRNA表达和蛋白合成水平明显下调(P<0.05)。结论大鼠AMI后LVNIZ CT-1mR-NA和蛋白的过度表达与AMI后LVRM的发生有联系,辛伐他汀可改善LVRM,其机制可能与抑制CT-1基因过度表达与蛋白合成有关。Aim To study the effect of simvastatin on cardiotrophin-1 （CT-1） expression after rats AMI in non-infarction zone in left ventricular （LVNIZ） and the left ventricular remodeling （LVRM） progression. Methods Male SD rats were divided into four groups （n = 8 ） ： AMI group, AMI ＋ Simvastatin group, Shamoperated group and normal group. Myocardial infarction model of the first two groups was established by ligation of left anterior descending coronary artery. AMI ＋ Simvastatin group was gavaged with simvastatin 40 mg·kg^-1·d^-1 Rats except Simvastatin treatment group were gavaged with part. aeq. 0.9% NaCl. After 4 weeks, the ratio of LV weight to body weight （LVWI）, the cross-sectional area of cardiomyocytes and the collagen volume fraction （CVF） were examined. The CT-1 mRNA expression in LVNIZ was determined by RT-PCR. The CT-1 protein production in LVNIZ was determined by Western blot. Results Compared with sham-operated rats and normal rats, left ventricular weight index （LVWI） , cardiomyocyte crosssectional area（CA） and CVF in LVNIZ were increased （P 〈 O. 05 ） in AMI group, the expression of CT-1 mRNA and production of CT-1 protein in LVNIZ increased obviously after AMI 4 weeks（P 〈 0.05 ）. CT-1 mRNA expression and protein production were all decreased in AMI ＋ Simvastatin group with lightened LVRM comparing with AMI group （ P 〈 0.05 ）. Conclusions There is significant correlation between overexpression of CT-1 mRNA and protein and LVRM after AMI. The mechanisms of simvastatin in preventing LVRM may be partly through depressing CT-1 mRNA expression and protein production.

关 键 词：心肌梗死 心肌营养素-1 心室重塑 辛伐他汀 

分 类 号：R-332[医药卫生] R322.11