肝细胞生长因子治疗心肌梗死后心力衰竭的实验研究

目的研究经冠状动脉转染携带人肝细胞生长因子(hepatocytegrowthfactor,HGF)的腺病毒(adenovirus,Ad5)对猪心肌梗死后心力衰竭的改善作用。方法12只苏中幼猪,随机分成转染Ad5-HGF组(治疗组)和转染未携带肝细胞生长因子的腺病毒载体(null-Ad5)组(对照组),每组6只。结扎前降支制成心肌梗死模型,手术后第4周及第7周时行冠状动脉造影和门控心肌灌注显像,评价侧支循环形成程度(Rentorp法)、心肌灌注及心功能的变化;用ELISA法检测肝细胞生长因子蛋白表达;以免疫组织化学法检测基因导入后平滑肌肌动蛋白抗体阳性(SMA )有灌注功能血管生成情况。结果经冠状动脉转染Ad5-HGF后心肌高度表达人HGF蛋白;治疗组心肌血流灌注及左心室射血分数(LVEF)较对照组明显改善;治疗组侧支循环形成明显增多,每平方毫米功能血管的数量明显高于对照组。结论经冠状动脉转染Ad5-HGF能使心肌高度表达HGF蛋白。HGF对梗死心肌的侧支循环形成、心肌灌注及心功能均有改善作用,能促进功能血管数增多。

Amelioration in cardiac function with Ad5-HGF transference in postinfarction heart failure swine

Objective To study the ameliorative effect on postinfarction heart failure of Ad_5-HGF (adenovirus-mediated human hepatocyte growth factor) in swine models. Methods Totally 12 young swine were randomly divided into 2 groups which were: Ad_5-HGF group (treatment group) and null- Ad_5 group (control group). At four weeks and seven weeks after left anterior descending coronary artery ligation in swine hearts, coronary angiography and Gate cardiac perfusion imaging were performed to evaluate the degree of collateral artery growth (Rentorp), cardiac perfusion, and heart function. The expression of HGF was examined by ELISA. Immunohistochemistry was performed to illustrate the angiogenesis of SMA~ vessels. Results (1) In comparison with the null- Ad_5 group, high expression of human HGF was observed in the myocardium of the Ad_5-HGF group. (2) The improvement in LVEF was more obvious in the Ad_5-HGF group than the control group in 7 weeks. Cardiac perfusion was significantly improved in the Ad_5-HGF group. (3) In the Ad_5-HGF group, growth of collateral blood vessels and also the number of SMA~ vessels per mm~2 were significantly greater. Conclusion (1) High expression of human HGF is observed in the myocardium through intracoronary transfection. (2) HGF can improve collateral artery formation and ameliorate heart function. (3) HGF can increase the number of vessels that are coated with SMC.