不同剂量氯沙坦对急性心肌梗死大鼠左室重构的干预作用

Comparison of effects of different does of Losartan in prevention of left ventricular remodeling after acute myocardial infarction in rats

目的对比不同剂量氯沙坦对AMI大鼠左室重构的防治作用,评价其量效关系,并与依那普利比较。方法雌性Wistar大鼠,随机抽取假手术组,其余结扎左冠状动脉致AMI模型。术后48h存活的123只随机分为：AMI对照组,依那普利组1.0mg/（kg·d）,氯沙坦高剂量组10mg/（kg·d）,氯沙坦中剂量组1.0mg/（kg·d）和氯沙坦低剂量组0.1mg/（kg·d）。给药治疗3周后均行血流动力学测定、心脏标本固定和病理分析。最终64只大鼠获完整资料,上述各组例数分别为9、8、13、13、11和10只。结果AMI各组梗死面积均在44.5%～46.8%,无显著差异（P〉0.05）。与假手术组相比,左室舒张末压（LVEDP）、左室实际和相对重量（LVAW和LVRW）、膨胀指数（EI）和重构指数（RI）均显著增加,变薄率（TR）显著降低（P均〈0.001）,发生了左室重构;而左室内压最大上升和下降速率（±dp/dtmax）显著降低（P均〈0.001）。与AMI对照组相比,氯沙坦高、中、低剂量组和依那普利组的LVEDP、LVAW、LVRW、EI和RI均显著降低或减少（P〈0.05～0.001）,TR显著增加（P〈0.05～0.001）;且高剂量氯沙坦组和依那普利组的LVEDP、-dp/dtmax、EI、TR和RI比低剂量氯沙坦组变化更显著（P〈0.05）。结论高、中、低剂量氯沙坦均能有效防治AMI大鼠的左室重构,低剂量有效,高剂量更优。

Objective To Compare the effects of different doses of Losartan in the prevention of left ventricular remodeling（LVRM）after acute myocardial infarction（AMI）in the rats,and to evaluate the dose-effect relation,and to compare with enalapril.Methods Sham-operated（n=12）were selected randomly to serve as non-infarction controls.AMI were made by ligating left coronary artery in female Wistar rats.48 hours after the procedure,the 123 surviving rats wre randomly divided into five groups of AMI controls and high-,middle-and low-dose Losartan and enalapril.Losartan and enalapril were delivered by direct gastric gavage.After 3 weeks of medical therapy,hemodynamic studies were performed in each group,and the rat heart were then fixed,and pathologic analysis were performed.Complete experimental data obtained in 64 rats were analyzed,comprising of sham-operated group（n=9）,AMI controls（n=8）,high-dose Losartan group（n=13）,middle-dose Losartan group（n=13）,low-dose Losartan group（n=11）,enalapril group（n=10）.Results There were no significant differences among the five AMI groups in MI size around 44.5%～46.8%（all P〉0.05）.Compared with sham-operated rats,the left ventricular end diastolic pressure（LVEDP）,absolute and relative weight（LVAW and LVRW）,expansion index（EI）,remodeling index（RI）in AMI group were all significantly increased（P〈0.05～0.001）,thinning ratio（TR）was significantly decreased（P〈0.05～0.001）,indicating that LVRM occurred after AMI.The maximun left ventricular pressure rising and dropping rates（±dp/dtmax）were all significantly reduced in AMI group（all P〈0.001）.Compared with the AMI group,LVEDP,LVAW,LVRW,EI and RI were all significantly decreased in all four treatment groups（P〈0.05～0.001）,TR were all significantly increased（P〈0.05～0.001）,and the LVEDP,EI,TR,RI and-dp/dtmax were all more significant in high-and middle-dose than in low-dose Losartan group（P〈0.05）.Conclusion High,middle and low dose of Losartan are all effective in preventing left ventricular remodeling after AMI in rats,with high and middle dose of Losartan being more effective.