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目的:研究经冠脉转染腺病毒(adenovirus,Ad5)携带的肝细胞生长因子(hepatocyte growth factor,HGF)对猪心肌梗死后心功能及心肌细胞凋亡的影响。方法:小型猪12只,随机分为对照组(null-Ad5,1ml)及转染Ad5-HGF治疗组(5×109Pfu/ml,1ml),每组6只。结扎前降支远端制作心肌梗死模型。术后4周,经右冠状动脉治疗组注射Ad5-HGF(5×109pfu/ml,1ml)、对照组注射null-Ad5(1ml)。两组均在手术后4周和7周行门控心肌灌注显像,评价心肌灌注及左室射血分数(LVEF)变化;并在7周时处死动物,TUNEL法观察心肌细胞凋亡,免疫组化评价Bcl-2及Bax蛋白表达。结果:①造模后4周治疗组和对照组之间心肌灌注及LVEF值无明显差异(P>0.05)。转染Ad5-HGF后3周,治疗组心肌灌注及LVEF值较治疗前明显改善(P<0.01),但对照组无明显变化(P>0.05),治疗组和对照组比较,心肌灌注及LVEF值均有明显增加(P<0.01);②在治疗组和对照组的移行区均可见心肌细胞凋亡,但治疗组心肌细胞凋亡指数明显低于对照组(P<0.01);③治疗组Bcl-2蛋白表达增加、Bax蛋白表达抑制,和对照组相比差异具有显著性(P<0.01)。结论:经非梗死相关动脉转染Ad5-HGF治疗能减少心肌细胞凋亡,改善心梗后心功能,其机制可能与Bcl-2表达上调和Bax表达下调有关。
Objective: To investigate the effects of hepatocyte growth factor (HGF) carried by adenovirus (Ad5) on the cardiac function and myocardial apoptosis in pigs after myocardial infarction. Methods: 12 miniature pigs were randomly divided into control group (null-Ad5, 1ml) and Ad5-HGF transfected group (5 × 109pfu / ml, 1ml), with 6 mice in each group. Before ligation, the distal branch was made into a myocardial infarction model. After 4 weeks, Ad5-HGF (5 × 109pfu / ml, 1ml) was injected into the right coronary artery and null-Ad5 (1ml) into the control group. Gated myocardial perfusion imaging was performed at 4 weeks and 7 weeks after operation to evaluate the changes of myocardial perfusion and left ventricular ejection fraction (LVEF). Animals were sacrificed at 7 weeks. The apoptosis of cardiomyocytes was observed by TUNEL method. Histochemistry was used to evaluate the protein expression of Bcl-2 and Bax. Results: ① There was no significant difference in myocardial perfusion and LVEF between treatment group and control group 4 weeks after model establishment (P> 0.05). Three weeks after transfection with Ad5-HGF, myocardial perfusion and LVEF in treatment group were significantly improved (P <0.01), but there was no significant change in control group (P> 0.05). Compared with control group, myocardial perfusion and LVEF (P <0.01). ②Apoptosis of cardiomyocytes was observed in transitional zone of treatment group and control group, but the apoptosis index of myocardial cells in treatment group was significantly lower than that in control group (P <0.01); ③The treatment group Bcl-2 protein expression increased, Bax protein expression was inhibited, compared with the control group, the difference was significant (P <0.01). Conclusion: Transfection of Ad5-HGF in non-infarcted artery can decrease cardiomyocyte apoptosis and improve cardiac function after myocardial infarction. The mechanism may be related to up-regulation of Bcl-2 expression and down-regulation of Bax expression.