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质粒介导下转染血管内皮生长因子基因不能防治小型猪冠状动脉再狭窄

Plasmid-Mediated Intravascular Local Transfer of Vascular Endothelial Growth Factor Gene Has no Effect on Restenosis of Coronary Artery in Mini-Swines

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【摘要】 目的 :评估质粒介导下蛋白涂层金属支架局部转染血管内皮生长因子 (VEGF)基因对小型猪冠状动脉再狭窄的作用。  方法 :选用 1 4只正常小型猪作为实验动物 ,载体为携带有VEGF基因的PcDNA3质粒。用常规球囊导管技术 ,将携带有VEGF基因的蛋白涂层支架置入冠状动脉前降支中段作为VEGF转基因组 (n =7) ,以相同方法置入单纯蛋白涂层支架作为对照组 (n =7) ,球囊与血管直径之比为 1 1∶1。在基因转染后 7天 ,行反转录聚合酶链反应和免疫组化染色。在支架置入后 3个月重复冠状动脉造影 ,测定管腔狭窄直径 ;同时行组织病理学检查。  结果 :支架被成功置入 1 4只动物冠状动脉前降支中段。支架置入后 7天 ,反转录聚合酶链反应结果证实 ,在转染部位的动脉壁内有VEGF信使核糖核酸的表达。免疫组化染色显示在中层平滑肌细胞浆内及外膜有VEGF蛋白质生成。在支架置入后 3个月重复冠状动脉造影显示 :转基因组和对照组均发生再狭窄 ,平均管腔狭窄直径分别是 ( 6 9±1 0 ) %和 ( 80± 1 4 ) % ,无显著性差异 (P =0 2 4 7)。组织病理学形态分析结果显示 :转基因组和对照组 ,在平均损伤积分、新生内膜厚度、平均新生内膜面积、百分狭窄面积和内膜 /中膜值等各项参数上均无显著性差别。  结论 :在本实验的再狭窄动物模

【Abstract】 Objective:To assess the effects of local vascular endothelial growth factor (VEGF)transfer using protein coated metallic stents on restenosis of coronary arteries in mini swine model. Method:A plasmid vector PcDNA3 carrying VEGF gene was used in this study.The coated stents carrying VEGF gene were implanted into left anterior descending branch of coronary arteries(LAD)in 7 mini swines.The other coated stents without carrying the gene were implanted into another 7 mini swine coronary arteries.All stents were implanted into the middle segment of LAD using balloon inflated to 10atm.The ratio of balloon to vessel diameters was 1 1∶1. RT PCR and immunohistochemical staining were completed 7 days after gene transfer.To determine whether VEGF gene inhibits smooth muscle cell proliferation,coronary angiography was repeated,followed by pathologic examination and morphometric analysis 3 months after stent implantation.Neointimal area(mm 2),neointimal thickness(mm),percent area stenosis,lumen diameter stenosis and I/M were analyzed using a computerized imaging system. Results:RT PCR and immunohistochemical staining confirmed the expression of VEGF mRNA expression and the presence of VEGF protein in the site of gene transfer.Restenosis developed in all animals including those in the VEGF group and control group.Lumen diameter stenosis were (69±10)% in VEGF group and (80±14)% in control group( p =0 247).Morphometric analysis showed that the mean injury grade,neointimal thickness,mean neointimal area,mean percent area stenosis and I/M had no significant differences between the two groups. Conclusions:The animal model of restenosis was successfully produced by oversized stent.Protein coated stent locally delivered VEGF gene to stenting site,but no effect on preventing restenosis following PTCA observed in this study.

【关键词】 基因支架质粒
【Key words】 GeneStentPlasmid
  • 【文献出处】 中国循环杂志 ,Chinese Circulation Journal , 编辑部邮箱 ,2002年05期
  • 【分类号】R541.4
  • 【被引频次】10
  • 【下载频次】74
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