[1]吕瑾,刘增长,张全军,等.ACE2过表达对大鼠心肌梗死后心室重构的影响[J].第三军医大学学报,2013,35(16):1680-1684.
 Lyu Jin,Liu Zengzhang,Zhang Quanjun,et al.Effect of overexpression of angiotensin converting enzyme 2 on ventricular remodeling after myocardial infarction in rats[J].J Third Mil Med Univ,2013,35(16):1680-1684.
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ACE2过表达对大鼠心肌梗死后心室重构的影响(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
35卷
期数:
2013年第16期
页码:
1680-1684
栏目:
论著
出版日期:
2013-08-30

文章信息/Info

Title:
Effect of overexpression of angiotensin converting enzyme 2 on ventricular remodeling after myocardial infarction in rats
作者:
吕瑾刘增长张全军范晋奇苏立殷跃辉
重庆医科大学附属第二医院心血管内科
Author(s):
Lyu Jin Liu Zengzhang Zhang Quanjun Fan Jinqi Su Li Yin Yuehui
Department of Cardiology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010,China
关键词:
心肌梗死血管紧张素转换酶2基质金属蛋白酶9心室重构
Keywords:
myocardial infarction angiotensin converting enzyme 2 matrix metalloproteinase 9ventricle remodeling
分类号:
R394.2;R364.33;R542.22
文献标志码:
A
摘要:
目的      探讨携带ACE2基因的重组腺病毒载体(Ad-ACE2)转染对大鼠心肌梗死(MI)后心室重构的影响及其机制。      方法      Sprague-Dawley(SD)大鼠75只,8~10周龄,体质量200~250 g,结扎左冠状动脉前降支,建立SD大鼠MI模型,完全随机分为心梗组(MI组)、生理盐水组(NS组)、空载体组、Ad-ACE2组(转染Ad-ACE2组),并另设假手术组(n=15)。NS组、空载体组、Ad-ACE2组分别以直接心肌内注射方式沿梗死周边区选取5个点注射NS、Ad-EGFP及Ad-ACE2,假手术组及MI不予以任何注射。术后4周检测并评价相关指标。      结果      ①与假手术组比较,Ad-ACE2组ACE2蛋白表达增加(P<0.05)。②与MI组比较,Ad-ACE2组肌纤维排列紊乱,肌丝断裂,细胞核固缩、碎裂等现象明显减轻;Ⅰ、Ⅲ型胶原表达均减少。③免疫组化与ELISA结果显示:与假手术组比较,MI组、NS组、空载体组及Ad-ACE2组AngⅡ、Ang-(1-7)蛋白表达均增高(P<0.05);与MI组比较,Ad-ACE2组AngⅡ蛋白表达降低(P<0.05),Ang-(1-7)蛋白表达增高(P<0.05)。④免疫印迹结果显示:与MI组比较,Ad-ACE2组MMP-9蛋白表达降低(P<0.05),TIMP-1蛋白表达水平增加(P<0.05),且MMP-9/TIMP-1的比值降低。⑤与假手术组比较,MI组、NS组、空载体组的TGF-β和α-SMA表达增高(P<0.05),而Ad-ACE2组表达降低(P<0.05)。      结论      过表达ACE2可改善心肌纤维化,缓解心室重构,其机制可能与其调节肾素-血管紧张素系统,下调MMP-9、TGF-β及α-SMA的表达,维持MMP-9/TIMP-1的比例平衡有关。
Abstract:
Objective      To determine the effect of adenovirus-angiotensin converting enzyme 2(Ad-ACE2)on the ventricular remodeling after myocardial infarction (MI) in rats.       Methods      A total of 75 Sprague-Dawley(SD) rats, at an age of 8 to 10 weeks, weighing 200 to 250 g were randomly divided into MI model group (n=60) and sham operation group (n=15). MI model was induced by the ligation of the anterior descending branch of left coronary artery. Then the MI rats were randomly treated with normal saline, vector, and Ad-ACE2, with 15 rats in each group. The left 15 MI rats served as model control. The rats from above treatment groups were injected intramyocardial directly into normal saline, Ad-EGFP and Ad-ACE2 in 5 different points along the infarct borders respectively. Rats in the model group and sham operation group received no such injection. The relative ventricular remodeling indexes after 4 weeks were evaluated.       Results      Compared with sham operation group, ACE2 protein was highly expressed in Ad-ACE2 group(P<0.05). The changes of muscle fiber disorder, myofilament fracture, nuclear condensation, and nuclear fragmentation, and the elevated expression levels of type Ⅰand Ⅲcollagens in the model control were improved significantly, and decreased in Ad-ACE2 group. Immunohistochemical staining and ELISA indicated the expression levels of AngⅡ and Ang-(1-7) were increased in MI, normal saline group, vector and Ad-ACE2 groups than in the sham operation group (P<0.05), and that of AngⅡwas decreased, while that of Ang-(1-7) protein was increased in Ad-ACE2 group than in MI group(P<0.05). Western blotting showed that Ad-ACE2 injection resulted in an obvious decrease in the MMP-9 expression, a significant increase in the TIMP-1 expression, and a following reduce in the ratio of MMP-9/TIMP-1 when compared with MI control(P<0.05). Compared with sham operation group, the protein levels of TGF-β and α-SMA were consistently increased in MI group, normal saline group and vector group, and decreased in Ad-ACE2 group(P<0.05).       Conclusion      The over-expression of ACE2 ameliorates ventricular fibrosis and attenuates ventricular remodeling after MI, which probably through regulating renin-angiotensin system, down-regulating MMP-9, TGF-β, and α-SMA, and maintaining the balance of MMP-9/TIMP-1.

参考文献/References:

吕瑾, 刘增长, 张全军, 等. ACE2过表达对大鼠心肌梗死后心室重构的影响[J].第三军医大学学报,2013,35(16):1680-1684.

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更新日期/Last Update: 2013-08-02