肝细胞生长因子对心肌梗死后左心室收缩同步性的影响  

Effect of hepatocyte growth factor on left ventricle contraction following myocardial infarction

作　　者：杨庭树[1] 李萍[1] 李岩密[1] 梁丽玲[1] 张华威[1] 易军[1] 苟朋[1] 

机构地区：[1]解放军总医院心内科,北京市100853

出　　处：《中国组织工程研究与临床康复》2008年第2期248-253,共6页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：军队"十五"重点课题资助(01Z036)~~

摘　　要：目的:实验证实肝细胞生长因子可以促进心肌梗死后侧支循环形成,减少梗死面积,改善心脏功能。拟验证肝细胞生长因子(Hepatocyte growth factor,HGF)对急性心肌梗死后左心室重塑的影响。方法:实验于2005-06/2006-03在解放军总医院心内科实验室完成。①实验材料:pc-DNA3-HGF基因由军事医学科学院王立山副教授馈赠;杂种犬13只,雌雄不限,体质量15～20kg。②实验分组:结扎犬左冠状动脉前降支复制急性心肌梗死模型,将造模成功的12只犬随机分为治疗组和对照组,每组6只。③实验过程:治疗组于梗死心肌周围注射pc-DNA3-HGF1mL(约300μg),对照组给予等量的生理盐水。④实验评估:分别于术后1,4,8周进行超声心动图检查,检测心功能、左室重塑指标。术后8周麻醉后处死动物,取出心脏,测量心脏及左心室重量,取心肌组织行苏木精-伊红染色;天狼猩红染色,并用图像分析系统测定梗死区、非梗死区及右室Ⅰ,Ⅲ型胶原含量;血管内皮细胞特异性Ⅷ因子免疫组织化学染色分析梗死区、非梗死区以及梗死边缘区血管生成情况;原位末端标记法染色观察细胞凋亡情况。实验过程中对动物处置符合动物伦理学标准。结果:①术后4周时,肝细胞生长因子治疗组左心室射血分数明显高于对照组(P<0.05);8周时,左心室射血分数明显升高,左心室收缩末容积较对照组降低(P<0.05)。②心肌梗死后8周时治疗组左房面积、二尖瓣返流面积以及二尖瓣返流面积与左房面积的比值均低于对照组,心脏及左室重量指数亦低于对照组,但无统计学意义(P>0.05)。③苏木精-伊红染色可观察到治疗组梗死心肌周围毛细血管较对照组增多,而对照组瘢痕形成明显。④Ⅷ因子免疫组织化学染色显示治疗组梗死边缘区毛细血管明显多于对照组(P<0.01);非梗死区毛细血管密度高于对照组(P=0.05)。⑤原位末端标记法染色显示与对照组�AIM： Hepatocyte growth factor （HGF） is proved to promote the formation of collateral circulation, reduce the infarction area and improve the heart function after myocardial infarction. This study is designed to investigate the effect of HGF on left ventricular remodeling caused by acute myocardial infarction. METHODS： The experiment was carried out in the Laboratory of Cardiology, Chinese PLA General Hospital from June 2005 to March 2006.（1）pc-DNA3-HGF gene was provided by Professor Wang Li-shan from the Academy of Military Medical Sciences, as a gift; 13 hybrid canines of either gender were used, weighed 15-20 kg.（2）Ligation of proximal left anterior descending coronary artery was induced in 13 hybrid canines for acute myocardial infarction models. Then 12 successful animal models were randomized into HGF-group and control group, with 6 ones in each group.（3）Canines in HGF-group were injected with 1 mL pc-DNA3-HGF （about 300 μg） at the margin of infarcted myocardial, and control group was injected with equal volume of saline.（4）Cardiac function and left ventricular remodeling data were measured through echocardiograpby after 1, 4, 8 weeks of ligation. Animals were executed at 8 wceks postoperatively, then heart and left ventricle were weighed. Left ventricular myocardium specimens were obtained and stained with hematoxylin and eosin, with pierosirius red staining to assess the collagen content, immunohistochemical staining for the specific factor Ⅶ of vascular endothelial cells to count capillary density, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） staining to detect cell apoptosis. All the managements were in accordance with the ethnical standard of animals. RESULTS： （1）Compared with control group, left ventricular eject fraction in HGF-group increased obviously after 4 weeks of ligation （P 〈 0.05） and also significantly improved at 8 weeks （P 〈 0.05）. Moreover, left ventricular end-systolic volume in HGF-group decreased

关 键 词：肝细胞生长因子 心肌梗塞 心室功能 组织构建 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]