AVE0991改善大鼠心肌梗死后心室重塑和心功能

AVE0991 Attenuates Ventricular Remodeling and Protects Cardiac Function in Rats After Myocardial Infarction

目的观察血管紧张素(1-7)[angiotensin-(1-7),Ang-(1-7)]的非肽类似物AVE0991对大鼠心肌梗死后心室重塑和心功能的影响。方法 40只雄性Sprague-Dawley大鼠随机分成假手术组、模型组、AVE0991组和AVE0991+A-779组,分别施予假手术或冠状动脉左前降支结扎术,术后4周在超声下检测左心室短轴缩短率(LVFS)、射血分数(LVEF)等心功能指标以及心脏结构指标,并取心脏分别行Masson和HE染色,测量心脏梗死面积及心肌细胞直径。结果术后4周,心脏超声提示心肌梗死大鼠的收缩期和舒张期左心室内径(LVDs和LVDd)较假手术组明显增大,室间隔明显变薄,AVE0991可在一定程度上减轻室间隔的变薄,而LVDs和LVDd在模型组、AVE0991组和AVE0991+A-779组之间差异无显著性。心肌梗死大鼠LVFS及LVEF较假手术组均明显下降,而AVE099与模型组比较,LVFS(P<0.05)及LVEF(P<0.05)均有明显改善。左心室质量指数(LVMI)在模型组、AVE0991组和AVE0991+A-779组中明显增加,较假手术组差异有显著性,经AVE0991治疗后,LVMI较模型组有减轻(P<0.01)。HE染色显示,AVE0991组较模型组能明显减少心肌梗死后大鼠心肌细胞的直径(P<0.05)。Masson染色显示,AVE0991组大鼠心肌梗死面积较模型组略有下降(P<0.01)。而AVE0991以上的保护作用均可被Ang-(1-7)特异性受体抑制剂A-779抵消。结论 AVE0991能减轻大鼠急性心肌梗死后诱导的心室重塑,改善心功能,其作用可能通过Ang-(1-7)的Mas受体起作用。

Aim To investigate the beneficial effects of nonpeptide angiotensin-（1-7）[Ang-（1-7）] analogue AVE0991 on ventricular remodeling and cardiac dysfunction in rats induced by myocardial infarction（MI）. Methods Forty male Sprague-Dawley rats were randomly divided into sham operation group,control group,AVE0991 group and AVE0991 ＋ A-779 group. MI was induced by left coronary artery ligation. After 4 weeks of treatment,transthoracic echocardiography（TTE） was used to evaluate cardiac function. The left ventricle wet weight was recorded,normalized for body weight. Left ventricle serial sections were dyed with Masson or hematoxylin-eosin（HE） stain to quantify the infarct size and diameter measurement of cardiomyocytes.Results Four weeks after MI,rats with MI demonstrated significantly increase in the left ventricular end-diastolic（LVDd） and end-systolic dimension（LVDs） and decrease in interven-tricular septum end-systolic（IVSs） and end-diastolic thickness（IVSd）,left ventricular fractional shorting（LVFS） and leftventricular ejection fraction（LVEF）.AVE0991 treatment attenuated the decrease in LVFS（25.5 %±7.3 % vs18.4 %±3.3 %,P0.05） and LVEF（44.8%±7.6% vs 32.7%±6.5 %,P0.05） compared to control group.AVE0991 also reduced MI-induced hypertrophy as quantified by myocyte diameter measurements（vs control group,17.6±2.4μm vs 22.9±3.9μm,P0.05）.In addition,left ventricular mass index（LVMI）（2.54±0.25 vs 2.93±0.34,P0.01） and infarct size（42.6 %±3.6 % vs 50.9 %±4.4 %,P0.01） were slightly reduced in AVE0991group compared to control group.In addition,the specific antagonist for Ang-（1-7）,[D-Ala7]-Ang-（1-7）（A-779）,showed a tendency to diminish the protective effects of AVE0991.Conclusion AVE0991 could attenuate ventricularremodeling and improve cardiac function induced by acute myocardial infarction in rats,its effects may play a role through thespecific Mas receptor for Ang-（1-7）.