重组人生长激素影响急性心肌梗死大鼠心功能的实验研究

Effect of recombinant growth hormone on function 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)大鼠心功能的影响,并探讨其可能的机制。方法采用结扎大鼠左前降支的方法制备急性心肌梗死大鼠模型。术后24h存活大鼠随机分为单纯心肌梗死组(MI组)。GH1组:术后24h开始皮下注射rhGH 0.2mg.kg-1.d-1;GH2组:术后24h开始皮下注射rhGH 1.0mg.kg-1.d-1。另设假手术组(SO组)为对照组,连续处理28d后,利用多普勒心脏彩超观察各组心功能;通过TTC染色观察各组梗死面积,通过Ⅷ因子免疫组织化学染色测定rhGH对AMI大鼠缺血心肌微血管密度的影响;透射电镜下观察各组大鼠缺血心肌超微结构。结果GH2组AMI大鼠心脏功能显著改善,而且未发现明显的左室肥厚。GH1组AMI大鼠心功能改善不明显。GH2组心肌梗死面积显著减小〔(24.83±6.05)与(32.89±5.13),差异有统计学意义(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),差异有统计学意义(P<0.05),(28.5±3.6)与(11.2±2.79),差异有统计学意义P<0.01)〕。GH2组较GH1组效果更加明显〔(28.5±3.6)与(19.8±2.9),差异有统计学意义(P<0.01)〕。与MI组大鼠相比,GH1组大鼠缺血心肌心肌细胞超微结构有所改善,GH2组则有明显好转。结论适当剂量的rhGH可以最终改善AMI大鼠心脏功能,其作用机制可能与促进血管再生达到一定程度,从而有效保护心肌细胞、减轻心肌细胞坏死、减小心肌梗死面积有关。

Objective To observe the effect of recombinant growth hormone on function of acute myocardial infarction rats and its possible mechanism. Methods Ninety male Sprague-Dawley rats weighing approximately 150-200g were subjected to left anterior descending coronary artery ligation or sham operation（SO）. 24h after surgery, the survive rats were randomized to receive recombinant human growth hormone 0.2mg·kg^-1·d^-1 （GHlgroup n= 16） or 1.0mg·kg^-1·d^-1 （GH2 group n=15） or nothing （MI group n= 16）. Additional rats（n = 19） underwent thoracic incision without ligation of left anterior descending coronary artery to serve as age-matched sham operated controls（SO,n= 13）. the cardiac function were evaluated by Doppler ehocardiographic; infarct size was caculated by TTC stain. Collateral microvessel density were measured by Ⅷ factor immunohistochemical analysis cardial cell strusture were compared under transmission electron microscopy. Results The treatment with rhGH following AMI resulted in increasing microvassel density in both G Hland GH2groups campare with MI group[（19.8±2.9） vs （11.2±2.79）, P〈0. 05, （28. 5±3.6） vs （11.2±2.79）, P〈 0.001 respectively], myocardial cells protection , better cardiac cell structure, reduction of myocardial infarction area [（24. 83±6. 05） vs （32.89±5.13）,P〈0.01 compared with MI group]and preservation of cardiac function were observed,while not found in GH1 group. Conclusion A certain dose of recombinant human growth hormone can promote cardiac function of AMI rats. It may be due to the angiogenesis reached a certain level by the administration of rhGH , protect acute myocardial infarction rats＇ cardiac cells , reduce myocardial infarction area.