MMP-2对大鼠心肌梗死后心肌Ⅰ、Ⅲ型胶原表达的影响及洛沙坦的干预效应  

Effect of losartan on ventricular remodeling induced by matrix metalloproteinase-2 after myocardial infarction in rats

作　　者：陈昭喆 宋亚辉 谢秀乐 袁俊强 孙向东 

机构地区：[1]河南省信阳市中心医院心内科,464000

出　　处：《重庆医学》2007年第12期1173-1174,1178,共3页Chongqing medicine

摘　　要：目的研究大鼠心肌梗死后基质金属蛋白酶-2(MMP-2)对心肌Ⅰ、Ⅲ型胶原表达的影响及洛沙坦的干预作用。方法结扎SD大鼠冠状动脉前降支复制急性心肌梗死模型,随机分成心肌梗死对照组(n=26)和洛沙坦治疗组(n=24)(30mg.kg-1.d-1)。两组又随机分为1周、2周和4周亚组。另设假手术组(n=8)。应用超声心动图及病理学方法测定胶原的表达以评价大鼠心功能变化和心室重塑的过程。用免疫组化方法检测MMP-2蛋白表达及Ⅰ、Ⅲ型胶原表达情况。结果与假手术组相比,心肌梗死对照组MMP-2各时间点亚组蛋白表达均增高(均P<0.05)。非梗死区Ⅰ/Ⅲ型胶原比例在2周和4周随之升高(均P<0.05)。而洛沙坦治疗组MMP-2蛋白表达在1周、2周和4周亚组,均较心肌梗死对照组显著降低(均P<0.05),Ⅰ/Ⅲ型胶原比例在2周和4周亚组也较之显著降低(均P<0.05)。结论洛沙坦可通过抑制MMP-2的表达、逆转Ⅰ/Ⅲ型胶原比例改善心肌梗死后心室重塑。Objective To study the effect of the MMP-2 on the protein expression of Ⅰ,Ⅲ collagen following myocardial infarction in the rats and the intervening effects of losartan. Methods One hundred and ten adult male Sprague -Dawley rats underwent the left descending coronary artery ligation,then were divided randomly into AMI control group（26 cases）and AMI losartan treatment group（24 cases）（30mg · kg^-1 · d^-1 ） . The rats in these two groups were redivided into 3 sub-groups according to the course of treatment： 1-week,2-week, 4-week sub-groups. Eight rats underwent sham operation,and were killed after 4w. Cardiac function and ventricular remodeling were evaluated by echocardiography and morphological examination. The protein expression of Ⅰ,Ⅲ collagen was assessed by the method of immunohistochemical stain. The protein expression of MMP-2 was examined by immunohistochemistry. Results Compared with sham operated rats,the protein expression of MMP-2 were enhanced in all subgroups （all P〈 0.05）. The Ⅰ/Ⅲ collagen ratio in the noninfarcted myocardium increased subsequently at 2,4 week（all P〈0.05）. In comparison with the AMI control group, the protein expression of MMP-2 were significantly lower in the 2-week and 4-week sub-groups of losartan group（all P〈0.05）. Ⅰ/Ⅲ collagen ratio were also significantly decreased in the 2-week,4-week sub-groups of the losartan group （all P〈0.05）. Conclusion MMP-2 play,a key role in postinfarction extracellular matix remodeling. Losartan can prevent ventricular remodeling by suppressing the enhanced expression of MMP-2 and reversing the ratio of Ⅰ/Ⅲ collagen.

关 键 词：基质金属蛋白酶-2 心肌梗死 洛沙坦 

分 类 号：R542.22[医药卫生—心血管疾病]