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

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。

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

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,Sham-operated 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 cross-sectional area(CA)and CVF in LVNIZ were increased(P<0.05)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.