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肝细胞生长因子抑制慢性缺血性心脏病心肌纤维化及心肌细胞凋亡的实验研究
引用本文:陈安平,曾志勇,徐驰,杨鲸蓉,叶仕新,袁杨,黄盛东.肝细胞生长因子抑制慢性缺血性心脏病心肌纤维化及心肌细胞凋亡的实验研究[J].心脏杂志,2012,24(5):578-582.
作者姓名:陈安平  曾志勇  徐驰  杨鲸蓉  叶仕新  袁杨  黄盛东
作者单位:(1.南京军区福州总医院心胸外科,福建 福州 350025;
基金项目:南京军区医学创新课题资助(99MA095)
摘    要:目的:研究肝细胞生长因子(HGF)抑制慢性缺血性心脏病心肌纤维化及心肌细胞凋亡的作用。方法: 采用磷酸钙/DNA-TPC方法构建携带HGF基因的重组腺病毒(Ad.HGF)。经18只小型猪的左胸冠状动脉回旋支放置Ameroid环建立慢性心肌缺血猪动物模型,并随机分为3组即盐水组、AdHGF组和缺陷型空病毒Ad5(AdNull)组,每组6只(n=6)。于缺血心肌处,分别注射4×109 pfu 200 μl AdHGF、4×109 pfu 200 μl AdNull及200 μl盐水。4周后做超声心动图检查各组的心脏功能,并行病理学心肌纤维化、心肌凋亡检测。结果: 心脏彩超检测显示,AdHGF组室壁增厚,运动增加,左室舒张末容积(LVEDV)、左室射血分数(LVEF)及短轴缩短率(FS)等明显改善(P<0.05)。AdHGF组心肌组织切片缺血坏死区纤维组织增生明显低于AdNull组(P<0.05)。AdHGF组心肌中Ⅲ型胶原蛋白的量明显低于AdNull组(P<0.05)。AdHGF组心肌细胞的凋亡率(%)明显低于对照组(P<0.05)。结论: HGF具有抑制慢性缺血性心脏病心肌纤维化及心肌细胞凋亡的作用,从而可抑制心室重构和改善心功能。

关 键 词:慢性缺血性心脏病    肝细胞生长因子    纤维化    细胞凋亡    小型猪
收稿时间:2012-04-27

Experimental study of hepatocyte growth factor in inhibition of myocardial fibrosis and apoptosis of chronic ischemic heart disease
CHEN An-ping,ZENG Zhi-yong,XU Chi,YANG Jing-rong,YE Shi-xin,YUAN Yang,HUANG Sheng-dong.Experimental study of hepatocyte growth factor in inhibition of myocardial fibrosis and apoptosis of chronic ischemic heart disease[J].Chinese Heart Journal,2012,24(5):578-582.
Authors:CHEN An-ping  ZENG Zhi-yong  XU Chi  YANG Jing-rong  YE Shi-xin  YUAN Yang  HUANG Sheng-dong
Affiliation:1.Department of Cardiothoracic Surgery,Fuzong General Hospital,Nanjing Military Area command,Fuzhou 350025,Fujian,China;2.Department of Cardiothoracic Surgery,Changhai Hospital,Second Military Medical University,Shanghai 20043,China)
Abstract:AIM:To study the effects of hepatocyte growth factor (HGF) in inhibiting myocardial fibrosis and apoptosis after chronic ischemia myocardium. METHODS: AdHGF was established by calcium phosphate/DNA-TPC and the porcine model of chronic myocardial ischemia was established by placing an Ameroid ring inside the left circumflex coronary artery. The pigs were randomly divided into three groups (n=6) and were injected, respectively, with 4×109 pfu 200 μl AdHGF, 4×109 pfu 200 μl AdNull and 200 μl Ns in the ischemic myocardium. After 4 weeks, cardiac function was examined using cardio-ultrasound and myocardial pathology test was conducted. RESULTS: Echocardiography showed that the ventricular wall in AdHGF group was thickened and LVEDV, LEEF and FS were significantly improved (P<0.05). The myocardial tissue slice showed that the fibrous proliferation of pathological cardiac ischemia and necrosis in AdHGF group was significantly lower than that in AdNull group (P<0.05). Collagen type III protein and myocardial cells apoptosis rate in AdHGF group were significantly lower than those in control group (both P<0.05). CONCLUSION: HGF inhibits myocardial fibrosis and apoptosis after chronic ischemia myocardium and, consequently, inhibits ventricular remodeling and improves cardiac function.
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