重组人生长激素促进急性心肌梗死大鼠缺血心肌血管再生的实验研究

Study of recombinant human growth hormone on angiogenesis of acute myocardial infarction rats

目的观察重组人生长激素(recombinant human growth hormone,rhGH)对急性心肌梗死(acute myocardial infarc-tion,AMI)大鼠缺血心肌血管再生的影响。方法制备急性心肌梗死大鼠模型,将存活大鼠随机分为单纯心肌梗死组,GH1组:术后24h开始rhGH皮下注射0.2mg.kg-1.d-1,GH2组:术后24h开始rhGH皮下注射1.0mg.kg-1.d-1。另设假手术组为对照组,注射28d后处死动物,TTC染色法测定各组心肌梗死面积,Ⅷ因子免疫组织化学法测定缺血心肌微血管密度,RT-PCR及Western blot检测与AMI大鼠缺血心肌促血管再生相关的指标:VEGF、bFGF mRNA表达和蛋白合成。结果与MI组相比,GH1组与心肌梗死面积有减小的趋势,但无统计学差异;GH2组心肌梗死面积减小,差异有统计学意义(24.83±6.05与32.89±5.13,P<0.01);rhGH增加AMI大鼠缺血心肌微血管密度(19.8±2.9与11.2±2.79,P<0.05,28.5±3.6与11.2±2.79,P<0.01)。GH2组较GH1组效果更加明显(28.5±3.6与19.8±2.9,P<0.01)。rhGH促进AMI大鼠缺血心肌VEGF、bFGF mRNA表达及蛋白合成。结论较高剂量的重组人生长激素皮下注射可以有效减小急性心肌梗死大鼠心肌梗死的面积,而增加AMI大鼠缺血心肌VEGF、bFGF mRNA的表达和蛋白合成,进而促进缺血心肌血管再生可能是其机制之一。

Objective To study the effect of recombinant human growth hormone on angiogenesis in ischemic myocardium of acute myocardial infarction rats. Methods Sixty male Sprague-Dawley rats weighing approximately 150-200g were subjected to left accending coronary artery ligation. Twenty-four hours after surgery, the rats were randomized to receive recombinant human growth hormone0.2mg, kg^-1·d^-1（GH1,n=10） or 1.0mg· kg^-1·d^-1（GH2,n=10） or nothing（MI,n=11）.Additional rats（n=13） underwent thoracic incision without ligation of left accending coronary artery to serve as age-matched sham operated controls（SO,n = 13）. The infarct size was caculated by TTC stain;collateral microvessel density were measured by Ⅷ factor immunohistochemical analysis. VEGF and bFGF expression in ischemic myocardium of acute myocardial infarction rats was observed with RT-PCR and western blotting methods. Results As compared with control animals at 28d after ligation,GH2 treated rats had a significantly decreased infarct size,a higher expression of VEGF and bFGF , and a significantly higher collateral microvessel density either. Conclusion Recombinant human growth hormone can promote the angiogenesis in ischemic myocardium of acute myocardial infarction rats,increase the mRNA expression and protein synthesis of VEGF and bFGF,which may be due to reduce infarct size.