肝细胞生长因子对猪心肌梗死后心功能及心肌细胞凋亡的影响
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江苏省"135"工程重点医学人才基金资助(R2002043)


Effect on post-infarct heart function and apoptosis of cardiocyte with Ad5-HGF transference in swine
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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-Ad5,1 ml)及转染Ad5-HGF治疗组(5×109 Pfu/ml,1 ml),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 × 109 pfu/ml,1 ml)-对照组注射null-Ad5(1 ml)-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-

    Abstract:

    Objective:To investigate the effect on post-infarct heart function and apoptosis of cardiocyte with Ad5-HGF(adenovirus-mediated human hepatocyte growth factor) transference in swine models. Methods:Total 12 young swine were randomly divided into 2 groups, which were control group(null-Ad5,1 ml) and Ad5-HGF group(5 × 109 Pfu/ml,1ml). In four weeks after left anterior descending(LAD) coronary artery ligation,Ad5-HGF(5 × 109 Pfu/ml,1 ml)was transferred in the therapeutic group,and null-Ad5(1 ml) was transferred in the control group via right coronary artery. At 4th and 7th week after LAD ligation, gate cardiac perfusion imaging was performed to evaluate cardiac perfusion and LVEF. Swine were sacrificed in the 7th week,the apoptotic index of cardiocyte was observed by TUNEL, and the expression of Bcl-2 and Bax protein were evaluated by immunohistochemistry. Results:①In four weeks after LAD ligation,no difference was found between the control group and Ad5-HGF group in the cardiac perfusion and LVEF(P > 0.05). At three weeks after gene transfer,heart function was significantly improved in the Ad5-HGF group(P < 0.01), while unchanged in the control group(P > 0.05). The improvement of heart function was greater in the Ad5-HGF group than that in the control group(P < 0.01). ②TUNEL assay showed that there were lots of apoptotic cardioctyes in the border zone in two groups,but the Ad5-HGF group had a more obvious reduction in the apoptotic index, compared with the control group(P < 0.01). ③The expression of Bcl-2 protein was increased and the expression of Bax protein was inhibited in the Ad5-HGF group, compared with that of the control group(P < 0.01). Conclusion:Ad5-HGF transferred via noninfarct-related coronary artery could reduce apoptosis of cardiocyte and ameliorate post-infarct heart function. The up-regulation of Bcl-2 and down-regulation of Bax may play an important role in the anti-apoptotic effect of Ad5-HGF.

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张 胜,杨志健,王 伟,马东超,马文珠,曹克将.肝细胞生长因子对猪心肌梗死后心功能及心肌细胞凋亡的影响[J].南京医科大学学报(自然科学版),2008,28(8):959-963

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  • 收稿日期:2008-02-13
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