卡托普利对大鼠心肌梗死后肿瘤坏死因子-α和基质金属蛋白酶-2表达的影响

目的探讨卡托普利对心肌梗死后心力衰竭大鼠心肌肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-2(MMP-2)的表达以及心室重构和心室功能的影响。方法结扎大鼠冠状动脉前降支建立心肌梗死模型,术后24 h存活大鼠分为模型组和模型+卡托普利组(卡托普利500 mg.kg-1.d-1,饮水给药)。另设假手术组,假手术组和模型组大鼠饲普通饮水。术后6周免疫组织化学法检测TNF-α、Ⅰ型和Ⅲ型胶原,蛋白印迹法检测MMP-2,Van Gieson染色测胶原容积分数;压力传感器记录左心室血流动力学改变。结果与假手术组相比,模型组和模型+卡托普利组大鼠的心室功能明显降低(P<0.05),卡托普利能显著改善心肌梗死后心室功能(P<0.05);与假手术组相比,模型组和模型+卡托普利组非梗死区胶原容积分数(CVF)、Ⅰ/Ⅲ胶原比均升高(P<0.01),全心质量/体质量(THW/BW)及左心室实际质量/体质量(LVW/BW)显著增加(P<0.01);但卡托普利干预后CVF、Ⅰ/Ⅲ胶原比及THW/BW、LVW/BW均低于模型组(P<0.05)。与假手术组相比,模型组非梗死区MMP-2和TNF-α表达升高(P<0.01);卡托普利干预后MMP-2和TNF-α的表达明显低于模型组(P<0.01)。结论卡托普利能明显减轻大鼠心肌梗死后心室重构,改善心室功能,其作用可能与调节心脏TNF-α和MMP-2的表达有关。

Effect of captopril on the expression of tumor necrosis factor-alpha and matrix metalloproteinases-2in rats with myocardial infarction

Objective To investigate the effect of captopril on ventricular remodeling and cardiac function and the expression tumor necrosis factor-alpha（TNF-α）and matrix metalloproteinase-2（MMP-2）in rats with myocardial infarction.Methods Myocardial infarction model was established by ligation of the anterior descending coronary artery in rats.After 24 hours of operation,survival rats were randomly divided into model group,model＋captopril group（rats were treated with 500 mg·kg-1·d-1 captopril in their drinking water）,twelve rats in each group.Six rats were selected randomly without ligation as sham operation group.The sham operation group and model group were treated with water.Six weeks after operation,TNF-α and type Ⅰ and Ⅲ collagen were detected with immunohistochemistry;MMP-2 protein were detected by western-blot;Collagen volume fraction（CVF） was assessed with Van Gieson.Left ventricular haemodynamics changes were recorded with baroceptor.Results Compared with sham operation group,the left ventricular function of rats in model group and model ＋ captopril group were obviously degraded（P0.05）;Captopril could significantly improve ventricular function after myocardial infarction（P0.05）.CVF and typeⅠ/Ⅲ collagen ratio of non-infarct zone in model group and model ＋ captopril group were significantly higher than those in sham operation group（P0.01）;Total heart weight/ body weight（THW/BW） and left ventricular weight / body weight（LVW/BW） obviously increased（P0.01）.But the CVF,typeⅠ/Ⅲ collagen ratio,THW/BW and LVW/BW in model＋captopril group were significantly lower than those in the model group（P0.05）.The expression of TNF-α and MMP-2 in the non-infarcted zone of model group were significantly higher than those in sham operation group（P0.01）;But in model ＋ captopril group,the expression of TNF-α and MMP-2 were decresed compared with model group（P0.01）.Conclusion Captopril could lessen the left ventricular remodeling after myocardial infarction in rats and improves cardiac function.These effects could be relevant to regulate the expression of MMP-2 and TNF-α.