应用要点：①本试验通过犬心肌梗死后1，4，8周多个时间点，对其心脏功能及心室重塑动态发展过程进行了仔细的观察。②实验结果表明，急性心肌梗死后早期给予外源性肝细胞生长因子可改善犬心脏舒缩功能及心室重塑，其机制可能为肝细胞生长因子可以诱导血管生成，降低胶原沉积，抑制心肌细胞凋亡。

同行评价：文章探讨肝细胞生长因子对急性心肌梗死后左心室收缩同步性的影响。认为肝细胞生长因子可能通过抑制梗死后的胶原沉积，增加梗死心肌周围毛细血管数目，减少细胞凋亡，使心肌坏死及瘢痕形成减少，从而缓解急性心肌梗死心室重塑及心功能的恶化。具有较大的学术价值。

相关链接：由于心室重塑是一个长期的过程，既往研究已证实的单个时间点观察心肌梗死后心室重塑的过程具有很大的局限性。既往有很多实验证实心肌梗死后给予外源性促血管生长基因，可以通过增加侧支循环，减少梗死面积，改善心脏功能。

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15~20 kg。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-HGF 1 mL (约300 μg)，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相比，治疗组梗死边缘区凋亡细胞减少（P > 0.05）。
结论：肝细胞生长因子可能通过抑制梗死后的胶原沉积，增加梗死心肌周围毛细血管数目，减少细胞凋亡，使心肌坏死及瘢痕形成减少，从而缓解急性心肌梗死心室重塑及心功能的恶化。
关键词：肝细胞生长因子，心肌梗塞，心室功能，组织构建

杨庭树，李萍，李岩密，梁丽玲，张华威，易军，苟朋.肝细胞生长因子对心肌梗死后左心室收缩同步性的影响[J].中国组织工程研究与临床康复，2008，12(2):248-253 [www.zglckf.com/zglckf/ejournal/upfiles/08-2/2k-248(ps).pdf]

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

Abstract

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 2006.①pc-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.②Ligation 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.③Canines 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.④Cardiac function and left ventricular remodeling data were measured through echocardiography after 1, 4, 8 weeks of ligation. Animals were executed at 8 weeks postoperatively, then heart and left ventricle were weighed. Left ventricular myocardium specimens were obtained and stained with hematoxylin and eosin, with picrosirius red staining to assess the collagen content, immunohistochemical staining for the specific factor Ⅷ 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: ①Compared 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 at 8 weeks (P < 0.05).②Lowered left atrial area, mitral reflux area and the ratio (mitral reflux area/left atrial area) were observed in HGF-group than control group. And control group had higher heart and left ventricular weights (P > 0.05).③In HGF-group, neovascularization surrounding the infracted myocardial tissues and fewer scars was observed histologically.④Compared with control group, HGF-group showed higher capillary density at the margin of infarction area by Factor Ⅷ-related immunohistochemical staining (P < 0.01); so did the density in the non-infarction area (P =0.05).⑤TUNEL staining detected less apoptotic cells at the margin of infarction area in HGF-group (P > 0.05).
CONCLUSION: HGF can improve cardiac function and left ventricular remodeling after acute myocardial infarction by stimulating angiogenesis, reducing fibrosis and cardiocyte apoptosis, diminishing myocardiolysis and scarring.

Yang TS, Li P, Li YM, Liang LL, Zhang HW, Yi J, Gou P.Effect of hepatocyte growth factor on left ventricle contraction following myocardial infarction.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(2):248-253(China)
[www.zglckf.com/zglckf/ejournal/upfiles/08-2/2k-248(ps).pdf]