重组人生长激素对AMI大鼠缺血心肌VEGF表达的影响及其生物学效应

Effects of recombinant human growth hormone on VEGF expression in ischemic myocardium and angiogenesis of acute myocardial infarction rats

目的 探讨重组人生长激素对急性心肌梗死 (acutemyocardialinfarction ,AMI)大鼠缺血心肌VEGF表达的影响及其促血管再生的生物学效应。方法 制备急性心肌梗死大鼠模型 ,存活大鼠随机分为单纯心肌梗死组 (MI组 ) ,低剂量生长激素处理组 (GH1 组 :术后 2 4h开始rh GH皮下注射 0 2mg·kg- 1 ·d- 1 ) ,高剂量生长激素处理组 (GH2 组 :术后 2 4h开始rh GH皮下注射 1 0mg·kg- 1 ·d- 1 ) ,另设假手术组 (SO组 )为对照组 ,注射 2 8d后处死动物 ,采用Ⅷ因子免疫组织化学染色观察各组缺血心肌新生血管密度 ;RT PCR和蛋白免疫印迹方法各组大鼠缺血心肌VEGFmRNA表达和蛋白合成的影响。结果 与MI组相比 ,GH1 、GH2 组VEGFmRNA的表达和蛋白合成增加 ;GH1 、GH2 组缺血心肌血管密度增加 ( 19.8±2 9)比 ( 16.4± 4.4) 高倍视野 ,P <0 0 5 ;( 2 8.5± 3 .6)比 ( 16.4± 4.4) 高倍视野 ,P <0 0 0 1,GH2 组又明显高于GH1 组 (P <0 0 0 1)。结论 重组人生长激素可以促进急性心肌梗死大鼠缺血心肌血管再生 ,而增加缺血心肌VEGFmRNA的表达以及蛋白合成可能是其机制之一。

Objective To explore the effects of human recombinant growth hormone on the angiogenesis and the expression of vascular endothelial growth factor (VEGF) in ischemic myocardium of acute myocardial infarction (AMI) rats. Methods A total of 60 male Sprague-Dawley rats (150-200 g) were subjected to left ascending coronary artery ligation. At 24 h after ligation, the survived rats were randomized to receive recombinant human growth hormone at the dose of 0.2 mg·kg -1·d -1(GH1, n=10) or 1.0 mg·kg -1·d -1 (GH2, n=10) or nothing (MI, n=11). The left rats (n=13) underwent thoracic incision without ligation of the left ascending coronary artery to serve as age-matched sham-operation controls (SO, n=13). The rats were sacrificed at 28 d after the injection. The effects of recombinant human growth hormone on collateral microvessel density were measured by immunohistochemical analysis using Ⅷ factor. VEGF expression in ischemic myocardium of acute myocardial infarction rats was observed by RT-PCR and Western blotting. Results As compared with the control animals at 28 d after ligation, GH treated rats had significantly higher expressions of VEGF, and a significantly higher collateral microvessel density. Conclusion Recombinant human growth hormone can promote the myocardial angiogenesis. The increased mRNA expression and protein synthesis of VEGF in ischemic myocardium of acute myocardial infarction rats may be one of the mechanisms.