雷米普利对心肌梗死后室性心动过速大鼠基质重构的影响

Effect of Ramipril on extracellular matrix remodeling in rats with ventricular tachycardia after myocardial infarction

目的构建Wistar大鼠心肌梗死（MI）模型，利用血管紧张素Ⅰ转化酶抑制剂．雷米普利进行药物干预，观察其对MI后室性心动过速（VT）大鼠基质的影响。方法对成功行左前降支（LAD）结扎的Wistar大鼠（n=78只）随机分成两组：MI组和雷米普利（Ramipril）干预组。同时，选取12只LAD结扎未成功的大鼠作为对照组。第18周后对三组大鼠进行ECG监测，左心室腔内采血；利用ELISA（R＆D，USA）方法测定血清中肿瘤坏死因子（TNF-α）水平，同时采集心脏客观指标；再取MI边缘区或对照组相应区域的心室肌，通过电镜观察基质变化的情况。结果MI大鼠用雷米普利干预18周后，VT的发生数明显比MI组减少（P〈0．05），而且血清中TNF-α的下降幅度也较大（P〈0．05）。左心室最薄处和最厚处比值（min／max）在MI组与对照组间 有统计学意义（P=0．001），而在雷米普利组与对照组间无差异性。线性回归分析证实，在MI组和雷米普利组中的TNF-α水平与MI后VT发生有密切相关性（P=0．005）。电镜显示，MI组的心肌细胞间有大量的纤维细胞，基质细胞排列紊乱；雷米普利组的心肌细胞间基质排布相对整齐，且有线粒体生成；对照组的心肌细胞间仅有少量的纤维细胞，基质细胞排列整齐。结论雷米普利可能通过减少左室血清中TNF-α的含量，抑制心肌基质重构，从而降低VT发生的敏感性。

Objective To investigate the effect of angiotensin-Ⅰ converting enzyme inhibitor-Ramipril on ventricular extraceUular matrix （ECM） remodeling in the rat model of myocardial infarction （MI） with ventricular tachycardia （VT）. Method A total of 78 rats with successful hgation of left anterior descending branch of coronary artery were randomly divided into MI group and Ramipril group. At the same time, another 12 rats with failure of coronary artery ligation were regarded as a control group. After 18 weeks, electrocardiography was used to monitor all rats of three groups. The blood sample taken from left ventricle （LV） for measurement of serum TNF- α level by using ELISA （R＆D, USA） and cardiac functions of all rats were assessed by objective variables. In addition, LV muscle samples were taken from the borderline of infarction or the identical zone of rat heart in the control group, and these samples were observed with electron microscope. Results After 18 weeks, the occurrence of VT was significantly lower in rats of Ramipril group than that in the MI group （ P 〈 0.05）, and a greater decrease in tsemm TNF-α level was found in Ramipril group （ P 〈 0.05）. it was found that the ratio of min/max thickness of LV wall in rats of MI group was significantly different from that in rats of control group （ P = 0.001）, while there was no difference between Ramipril group and control group. Analysis of MI group and Ramipril group with linear regression showed the serum TNF-α level was closely related with VT after MI （ P = 0.005）. Examination of myocardium with electron microscope revealed a large number of fibrcytes and disordered matrix cells distributed among myocytes in the Migroup, and relatively ordered matrix cells and new-born mitochondria Ramipril group , while there were only few fibrocytes and ordered matrix cells among myocytes in the control group. Conclusion Ramipril may decrease the level of TNF-α in LV, and thereby inhibit the ECM remodeling after MI and in turn reduce the occurrence of VT.