卡托普利及合用氯沙坦对大鼠心肌梗死区早期重构影响的比较

Effect of captopril or combined with losartan on early remodeling of infarct zone of rats after acute myocardial infarction

目的:探讨急性心肌梗死(AMI)后早期联合应用卡托普利和氯沙坦对梗死区胶原沉积及梗死区扩张程度的影响及其机制.方法:56只雄性Wistar大鼠开胸结扎冠状动脉前降支建立AMI模型,术后24h内随机分为模型组,卡托普利组,卡托普利+氯沙坦组(合用组).卡托普利2g/L溶于动物饮用水中,自由饮水;氯沙坦20mg/(kg.d)灌胃.14d后经静脉注射100g/L氯化钾使心脏舒张期停跳,中性甲醛恒压灌注并固定左心室,直接测量心室容积后制做左心室横截面病理切片.行HE染色并用医学图像分析软件测定梗死面积、梗死区扩张指数;免疫组化方法测定梗死区I型胶原面密度、肌纤维细胞比例;每组另取6只大鼠以RT-PCR法测定梗死区Ⅰ,Ⅲ型胶原表达水平.结果:卡托普利或合用氯沙坦均显著降低梗死区扩张指数,但合用组梗死区扩张指数的改善劣于卡托普利组[(1.25±0.13vs1.12±0.14),P<0.05];合用组梗死区I型胶原面密度有低于模型组的趋势[(11.8±2.6)%vs(14.4±2.6)%],而卡托普利组无明显减低;合用组梗死区肌纤维细胞比例明显低于卡托普利组[(59.2±5.1)%vs(70.8±8.5)%,P<0.05],Ⅰ,Ⅲ型胶原的表达低于卡托普利组,分别为[(0.720±0.210vs0.996±0.162)和(0.488±0.113vs0.660±0.098),P<0.05].结论:AMI后早期联合应用卡托普利和氯沙坦,可降低梗死区胶原沉积,对梗死区早期扩张的抑制作用弱于单用卡托普利.

AIM： To evaluate the effect of losartan or combined with captopril on collagen accumulation and expansion of infarct zone in rats with acute myocardial infarction （AMI）, and the related mechanism. METHODS： Within 24 h after anterior descending coronary artery ligation, male Wistar rats were treated with placebo, captopril（2 g/L） ＋losartan[20 mg/（kg · d）], or captopril. 14 d later, the hearts were arrested by intravenous KCl injection（ 100 g/L）. The left ventricular（LV） was infused with phosphate-buffered formalin and fixed. LV volume was measured directly, and sections of LV were made. HE staining and image analysis system were used to measure infarct size and expansion index. Immunohistochemistry was used to evaluate the area density of type I collagen and the proportion of myofibroblasts in the infarct zone. The levels of type Ⅰ , Ⅲ collagens were measured by RT-PCR in the infarct zone. RESULTS： Both captopril and the combination of captopril and losartan decreased expansion index, but the effect of combination therapy tended to be inferior [ （1.12 ±0.14 vs 1.25 ±0.13）, P〈0.05]. Compared with the model group, the area density of type I collagen in the infarct zone was decreased in the combined treatment group[ （11.8 ± 2.6）% vs （ 14.4 ± 2.6） %], but not in the captopril treated group. In the infarct zone, the proportion of myofibroblasts was lower in combined treatment group than in captopril treated group [ （59.2 ± 5.1 ） % vs （ 70.8 ±8.5 ） % , P 〈 0.051 , and the gene expression of collagen al （Ⅰ/Ⅲ ） was decreased in combined treatment group than in captopril treated group [ （0.720±0.210 vs 0.996 ± 0. 162） and （0. 488 ± 0.113 vs 0.660 ± 0.098 ）, respectively, P 〈 0.05]. CONCLUSION： Adding losartan to effective captopril during the early period of AMI decreases collagen accumulation in infarct zone and attenuates its benefit on the expansion of infarct zone.