重组血管紧张素(1-7)基因转染对大鼠急性心肌梗死后细胞外基质重构的影响  

Effects of Ang-(1-7) gene transfection on ventricular remodeling in myocardial infarction rats

作　　者：朱晋坤[1] 毛华[1] 尹扬光[2] 董文[1] 邓梦扬[2] 鲁玉明[1] 熊宗华[1] 杜峰[1] 文美[1] 刘廷筑[1] 

机构地区：[1]贵阳市第一人民医院心血管内科,贵州550002 [2]第三军医大学新桥医院急诊科,重庆400037

出　　处：《第三军医大学学报》2014年第13期1380-1385,共6页Journal of Third Military Medical University

基　　金：贵州省科技厅基金项目(黔科合SY字[2009]3100)~~

摘　　要：目的观察重组血管紧张素(1-7)[angiotensin 1-7,Ang(1-7)]对大鼠急性心肌梗死(acute myocardial infarction,AMI)后细胞外基质重构的影响,并探讨其可能的分子机制。方法 40只成年雄性SD大鼠按随机数字表法分为4组:假手术组(SHAM)、心肌梗死组(MI)、报告基因组(MI+EGFP)和Ang(1-7)组[MI+Ang(1-7)],每组10只。采用冠状动脉结扎法建立大鼠AMI模型,MI+EGFP与MI+Ang(1-7)两组于心肌梗死周边区各选取5个点心肌内注射EGFP和Ang(1-7),SHAM组和MI组不予注射。术后4周测量心室质量/体质量、血流动力学;组织学方法评价心肌组织结构变化与胶原沉积;免疫组化检测Ang(1-7),Ⅰ、Ⅲ型胶原水平变化及蛋白印迹法检测MMP-2及TⅠMP-2的变化。结果①MI+Ang(1-7)组Ang(1-7)高效稳定表达,显著高于其余各组。②与SHAM组相比,MI与MI+EGFP两组心室质量/体质量,左室舒张末压,梗死周边区Ang(1-7),MMP-2,TIMP-2,Ⅰ、Ⅲ型胶原表达量及Ⅰ/Ⅲ型胶原比例均增加,而左室内压最大上升速率(dp/dtmax)和下降速率(dp/dtmin)显著下降(P<0.05)。③与MI及MI+EGFP组相比,MI+Ang(1-7)组Ang(1-7)、TIMP-2表达量及dp/dtmax、dp/dtmin明显增加,MMP-2,Ⅰ、Ⅲ型胶原表达量及Ⅰ/Ⅲ型胶原比例显著降低(P<0.05)。结论 Ang(1-7)显著改善大鼠急性心肌梗死后细胞外基质重构,其机制可能与通过上调TIMP-2,下调MMP-2蛋白表达相关。Objective To determine the effects of adenoviral gene transfer of angiotensin converting 1-7 （Ang-（1-7）） on the ventricular remodeling in rats with acute myocardial infarction （AMI） and investigate the possible protective mechanisms. Methods A total of 40 male Sprague-Dawley rats were randomly divided into 4 groups （n=10 for each group）, that is, sham operation group, MI group, AMI＋EGFP group and MI＋Ang-（1-7） group. AMI model were induced by ligation of the left anterior descending coronary artery. Rats in the MI＋EGFP and MI＋Ang（1-7） groups received an intra-myocardial injection of EGFP and Ang-（1-7）, respectively. Rats in the MI and sham operation groups received no injection intervention. In 4 weeks later, heart weight/body weight （HW/BW）, left ventricular end diastolic pressure （LVEDP）, dp/dtmax and dp/dtmin were examined. Myocardial structure changes and collagen deposition were evaluated histopathologically. The expression of Ang-（1-7）, MMP-2, TIMP-2, collagen type I and collagen type Ⅲ were measured by Western blotting and immunohistochemical staining. Results The protein expression of Ang-（1-7） was significantly higher in myocardial tissue in MI＋Ang-（1-7） group than the other groups. Compared with the sham operation group, the expression levels of Ang-（1-7）, MMP-2, TIMP-2, collagen type I and Ⅲ in the tissue around the infarct, and the ratio of collagen type Ⅰ to Ⅲ were increased, the ratio of ventricular/body weight and LVEDP were significantly higher, and dp/dtmax and dp/dtmin were significantly decreased in MI and MI＋EGFP groups. MI＋Ang-（1-7） group had significantly increased expression of Ang-（1-7） and TIMP-2, obviously elevated dp/dtmax and dp/dtmin, and markedly decreased MMP-2, collagen type Ⅰ and Ⅲ the ratio of collagen type Ⅰ to Ⅲ when compared with MI and MI＋EGFP group. Conclusion Ang-（1-7） significantly improves extracellular matrix remodeling after myocardial infarction, which may be related to up-re

关 键 词：心肌梗死 心室重构 血管紧张素1-7 基质金属蛋白酶 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学] R394.3[医药卫生—基础医学]