肝细胞生长因子在心肌梗死中促进血管新生的作用研究  

HGF promotes angiogenesis and improves coronary artery perfusion in a rabbit model of myocardial infarction

作　　者：韩金霞[1] 梁兆光[2] 呙锐锋[1] 孟玲丽 徐华[1] 赵悦[1] 李晶瑶 HAN Jin-xia;LIANG Zhao-guang;GUO Rui-feng;MENG Ling-li;XU Hua;ZHAO Yue;LI Jing-yao(Department of Cardiology,The General Hospital of Daqing Oil Field,Daqing 163000,China;Department of Cardiology,The First Affiliated Hospital of Harbin Medical University,Harbin 150001,China)

机构地区：[1]大庆油田总医院心内科,黑龙江大庆163000 [2]哈尔滨医科大学附属第一医院心内科,黑龙江哈尔滨150001

出　　处：《哈尔滨医科大学学报》2018年第2期110-114,共5页Journal of Harbin Medical University

基　　金：大庆市指导性科技计划项目(zdy-2016-052)

摘　　要：目的探讨肝细胞生长因子在心肌梗死中对心肌血管新生的促进作用,寻找改善心肌梗死区域供血的有效治疗方法。方法新西兰大白兔30只,随机分3组,每组10只,即A组(术前注射组):行冠状动脉结扎术并于术前30 h注射兔HGF质粒; B组(术后注射组):冠状动脉结扎术后即刻注射兔HGF质粒; C组(对照组):仅行冠状动脉结扎术。各组于术前、术后30 h、5 d、10 d、15 d、20 d、25 d、30 d分别采集外周血,用Western blot法检测血中HGF含量。术后10 w处死兔,采用免疫组化法检测缺血心肌周围CD34+表达,心肌缺血Nagar-Olsan特染光镜下观察心肌缺血面积和电镜下观察心肌梗死区域新生血管变化。结果 A组及对照组除术后30 h时间点外,其余各时点血中均未检测到HGF表达,而B组在术后30 h、5 d、10 d、15 d均检测到HGF表达。B组CD34+阳性表达明显高于A组和对照组(P <0. 05),A组与对照组CD34+的阳性表达无差异(P> 0. 05)。Nagar-Olsan特染光镜下B组心肌缺血面积明显小于A组和对照组。电镜下观察心肌梗死区域血管变化结果显示,与A组和对照组比较,B组血管内皮细胞轻度变性。结论心肌梗死后即刻注射兔HGF质粒,可以改善梗死区域心肌供血,促进血管新生,建立有效的侧支循环,从而减少心肌梗死的范围,而心肌梗死前注射兔HGF质粒达不到改善心肌缺血的作用。Objective To investigate the promoting effect of HGF on myocardial blood supply in a rabbit model of myocardial infarction. Methods Thirty New Zealand rabbits were ran- domly divided into three groups. Group A： Rabbit HGF plasmid expression vector was injected prior to the coronary artery ligation ; Group B ： The rabbit HGF plasmid was injected immediate- ly after the coronary artery ligation ; Group C （ control group） ： No injection of rabbit HGF plas- mid. Peripheral blood was obtained before the operative procedure and at 30 h, 5, 10, 15,20, 25 and 30 days following the procedure. Serum HGF levels were measured by RT-PCR. The expression of CD34^＋ was detected by immunohistochemistry. The area of myocardial in- farction was revealed using Nagar-Olsan specific stain for ischemic myocardial tissue, imaged under light microscopy, and quantified. Coronary artery endothelial cells were imaged by elec- tron microscopy. Results In groups A and C （control）, no expression of HGF was found ex- cept at 30 h after surgery, while HGF expression in group B was found at 30 h, 5, 10 and 15 days after surgery. CD34^＋ expression was substantially increased in group B compared with the control. In contrast, no difference in CD34^＋ expression was found between group A and group C. The area of myocardial infarction in group B was reduced compared with that found in group A and group C. Coronary endothelial cell proliferation was also greater in group B compared with the other two groups. Conclusion The injection of a rabbit HGF plasmid expression vec- tor into rabbits immediately following a surgically-induced myocardial infarction can stimulate angiogenesis to generate an effective bypass circuit of blood vessels in the coronary vasculature. The HGF-promoted neovascularization can improve myocardial blood supply and reduce the area of myocardial infarction. In contrast, the injection of HGF plasmid before the myocardial in- farction play no protective role.

关 键 词：肝细胞生长因子 心肌梗死 恤管新生 

分 类 号：R542.2[医药卫生—心血管疾病]