大鼠心肌梗死后螺内酯与氯沙坦干预对其心肌胶原变化的影响

Effect of Spironolactone and Losartan on Myocardium Collagen in Rats with myocardial Infarction

目的:观察大鼠急性心肌梗死(acute myocardial infarction,AMI)后左心室心肌重构分析和非梗死区Ⅰ、Ⅲ型胶原含量的变化,分别使用螺内酯和氯沙坦以及将两药合用对AMI模型进行干预,探索醛固酮受体拮抗剂和血管紧张素受体阻断剂对AMI后心室重构和胶原增生的影响。方法:将50只雌性SD大鼠随机分为AMI组、螺内酯组、氯沙坦组、联合用药组和假手术组,每组10只,结扎大鼠左前降支建立急性心肌梗死模型。术后8周进行血流动力学测定、病理分析和非梗死区Ⅰ、Ⅲ型胶原含量的测定。结果:AMI组与假手术组相比,左心室舒张末压(LVEDP)、容积、重量和非梗死区Ⅰ、Ⅲ型胶原含量均显著增加(P<0.05);左心室球形指数、左心室内压最大上升和下降速率(±dp/dt/LVSP)均显著降低(P<0.05)。螺内酯组与AMI组相比,左心室非梗死区Ⅰ、Ⅲ型胶原含量显著减少(P<0.05),其余各指标差异无统计学意义(P>0.05)。氯沙坦组和联合用药组与AMI组相比,LVEDP、左心室实际重量显著降低(P<0.05);左心室容积仅联合用药组有显著降低(P<0.05);而两组的±dp/dt/LVSP显著增加(P<0.05)。螺内酯、氯沙坦和联合用药3组与AMI组相比,左心室非梗死区Ⅰ、Ⅲ型胶原含量均显著减少(P<0.05);且3组之间差异无统计学意义(P>0.05)。结论:螺内酯能有效抑制AMI左心室非梗死区Ⅰ、Ⅲ型胶原的增生,提示螺内酯可能有改善左心室重构的潜在作用。氯沙坦与螺内酯合用可更有效防治AMI后左心室重构,改善左心室舒张功能。

Objective： To investigate the effect of spironolactone and losartan on ventricular myocardial remodeling and change of type I and Ⅲ of myocardium collagen in post-myocardial infarction rats. Methods： Fifty rats were randomized into 5 groups： AMI group, AMI＋spironolactone group, AMl＋losartan group, AMI＋combination group and sham-operation group. The models of AMI were ligated with anterior descending coronary artery; the sham-operation group was made by the same procedure without ligation. The rats were killed 8 weeks after operation to examine hemodynamic parameters, body weight （BW）, left and fight ventrieular weight（LVw, RVw） and changes of type I and Ⅲ of myocardium collagen. Results： Compared with the sham-operation group, the RVw/BW, LVw /BW, left ventricular en-diastolic pressure （LVEDP）, and CVF of type [ and type Ⅲ in the infracted zone and noninfareted zone of LV were all significantly increased in the AMI group（P〈0.05）, while the maximal rate of rise and fall（±dp/dt） and their adjustment by LVSP（±dp/dt/LVSP） were markedly decreased （P〈0.05）. There was no significant difference between spirolactone group and AMI group besides the type I and Ⅲ CVF in the noninfarcted zone of LV （P〉0.05）. Compared with AMI group, LVEDP, LV weight were significantly decreased in spirolactone group and combination group （P〈0.05）, and ±dp/dt/LVSP were increased in the two groups（P〈0.05）. Compared with AMI group, type I and Ⅲ CVF in the noninfarcted zone of LV were all significantly decreased in the spirohctone group, losartan group and the combination group （P〈0.05）. There was no significant difference between the three groups in decreasing collagen deposition in the noninfarcted zone （P〉0.05）. Conclusion： Spirohctone can effectively decrease the collagen deposition in the noninfarcted zone, and the combination of losartan and spirolactone can improve left ventricular remodeling and LV dilation.