目的 观察阿托伐他汀对大鼠急性心肌梗死(AMI)后心脏重构及心功能的影响,并探索其作用是否与转化生长因子-β1(TGF-β1)信号通路有关.方法 结扎64只雄性SD大鼠左冠状动脉构建AMI模型,存活45只随机分为3组,即对照组(n=15),低剂量阿托伐他汀组[n=15,10 mg/(kg·d)]及高剂量阿托伐他汀组[n=15,20 mg/(kg·d)],另设假手术组(n=15),术后24 h开始灌胃给药.8周后比较各组大鼠心功能、左室质量指数、胶原容积分数、TGF-β1及Smad2的mRNA及蛋白表达差异.结果 (1)对照组心功能显著低于假手术组(P＜0.05),左室质量指数、胶原容积分数、TGF-β1及Smad2的mRNA及蛋白表达均显著高于假手术组(P＜0.05)；(2)两个阿托伐他汀组的心功能均显著优于对照组(P＜0.05),左室质量指数、胶原容积分数、TGF-β1及Smad2的mRNA及蛋白表达均显著低于对照组(P＜0.05)；(3)高剂量阿托伐他汀组的作用更显著(P＜0.05).结论 阿托伐他汀可显著改善大鼠AMI后心脏重构及心功能,其作用具有剂量依赖性,其作用机制可能与抑制TGF-β1/Smad2信号通路有关.%Objective To investigate the effect of atorvastatin on cardiac remodeling and function after acute myocardial infarction (AMI) in rats and whether this effect is mediated by transforming growth factor-pi (TGF-β1) signaling pathway. Methods AMI was induced by left coronary artery ligation in 64 male Sprague-Dawley rats, and 45 surviving rats were randomized into control group (n=15), low-dose atorvastatin group (10 mg/kg, n=15) and high-dose atorvastatin group (20 mg/ kg, n=15). Similar surgical procedure was performed in sham-operated rats (n=15) without coronary ligation. Atorvastatin was given daily by gavage from the first day after AMI. Eight weeks later, the cardiac function, left ventricular weight/body mass index (LVMI), collagen volume fraction (CVF), and the expressions of TGF-β1 and Smad2 were compared between the groups. Results AMI caused significantly reduced cardiac function, increased LVMI and CVF, and upregulated expressions of TGF-β1 and Smad2 mRNA and proteins in the control group (P<0.05). The cardiac function, LVMI, and CVF were improved by atorvastatin, which also down-regulated the expressions of TGF-β1 and Smad2 (P<0.05), and the effects were more prominent in high-dose atorvastatin group (P<0.05). Conclusion Atorvastatin can dose-dependently improve cardiac remodeling and function after AMI in rats, which is mediated by regulating the activity of TGF-β1/Smad2 signaling pathway.
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