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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 investigate the effect of angiotensin 1-7 (Ang (1-7)] on extracellular matrix remodeling after acute myocardial infarction (AMI) in rats and to explore its possible Molecular mechanism. Methods Forty adult male Sprague - Dawley rats were randomly divided into 4 groups: SHAM group, MI group, MI + EGFP group and Ang (1-7) group [MI + Ang (1-7)], 10 in each group. AMI model was established by ligation of coronary artery in rats. MI + EGFP and MI + Ang (1-7) groups were injected intramuscularly with EGFP and Ang (1-7), SHAM and MI group not injection. The ventricular mass, body mass and hemodynamics were measured 4 weeks after operation. The changes of myocardial tissue structure and collagen deposition were evaluated by histological methods. The changes of Ang (1-7), collagen type Ⅰ and Ⅲ and Western blot were detected by immunohistochemistry The changes of MMP-2 and TⅠMP-2 were detected. Results ① The expression of Ang (1-7) in MI + Ang (1-7) group was efficiently and stably expressed, which was significantly higher than those in other groups. ②Compared with SHAM group, the expression of ventricular mass / body mass, left ventricular end diastolic pressure, Ang (1-7), MMP-2, TIMP-2, type I and type III collagen in MI and MI + And the ratio of type Ⅰ / Ⅲ collagen increased, while the maximum rate of dp / dtmax and dp / dtmin decreased significantly (P <0.05). ③ Compared with MI and MI + EGFP group, the expressions of Ang (1-7), TIMP-2, dp / dtmax and dp / dtmin in MI + Ang group were significantly increased Collagen expression and collagen type Ⅰ / Ⅲ ratio decreased significantly (P <0.05). Conclusion Ang (1-7) significantly improves the extracellular matrix remodeling after acute myocardial infarction in rats. The mechanism may be related to up-regulating TIMP-2 and down-regulating the expression of MMP-2.