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背景:血管内皮生长因子(Vascular endothelial growth factor,VEGF)能促进实验性动脉成形及支架置入后血管内皮迅速再生,使血栓形成减少,新生内膜厚度和管腔狭窄程度减轻。目的:在建立动脉粥样硬化兔模型基础上,观察局部转染VEGF基因对被扩张动脉内皮形成的影响。设计、时间及地点:随机对照动物实验,于2004-11/2006-11在华中科技科技大学同济医学院微生物实验室完成。材料:高脂饲养建立动脉粥样硬化兔模型,20只模型兔随机分为对照和基因治疗组两组,每组10只。方法:基因治疗组利用球囊导管扩张左肾动脉开口上段腹主动脉并导入pcDNA3.0载体介导的hVEGF165,对照组导入空载体。主要观察指标:术后1,2,4周MRI观察左肾动脉开口处上段被扩张腹主动脉的管腔面积。术后2,4周处死家兔取材,采用HMIAS-2000高清晰度彩色医学图文分析系统观察内膜面积/中膜面积比值,采用Ⅷ因子相关抗原免疫组织化学染色观察血管内皮细胞再生情况。结果:利用球囊导管能成功转导pcDNA3.0/hVEGF165。基因治疗组术后2,4周管腔面积大于对照组(P<0.05),内膜面积/中膜面积比值小于对照组(P<0.05);基因治疗组扩张血管内皮细胞再生在术后2周即完成,而对照组到4周才完成。结论:转导pcDNA3.0/hVEGF165基因能够促进局部血管内皮化,明显减轻再狭窄程度及内膜增厚。
BACKGROUND: Vascular endothelial growth factor (VEGF) can promote the rapid regeneration of vascular endothelium after experimental arterial angioplasty and stent implantation, resulting in the reduction of thrombus and the reduction of neointimal thickness and stenosis. OBJECTIVE: To establish a rabbit model of atherosclerosis and observe the effect of VEGF gene transfection on the formation of dilated artery endothelium. DESIGN, TIME AND SETTING: A randomized controlled animal experiment was performed at the Microbiology Laboratory, Tongji Medical College, Huazhong University of Science and Technology, 2004-11 / 2006-11. MATERIALS: A model of atherosclerosis rabbits was established by high fat diet. Twenty rabbits were randomly divided into control group and gene therapy group (n = 10). Methods: In the gene therapy group, the upper abdominal aorta of the left renal artery was expanded by balloon catheter and introduced into pcDNA3.0 vector mediated hVEGF165. The control group was introduced into empty vector. MAIN OUTCOME MEASURES: The lumen area of the dilated abdominal aorta in the upper part of the left renal artery was observed by MRI at 1, 2 and 4 weeks after operation. The rabbits were sacrificed at 2 and 4 weeks after operation. The ratio of intima / media area was determined by HMIAS-2000 high-resolution color medical image analysis system. The regeneration of vascular endothelial cells was observed by immunohistochemical staining of factor Ⅷ related antigen. Results: pcDNA3.0 / hVEGF165 was successfully transduced by balloon catheter. In the gene therapy group, the luminal area at 2 and 4 weeks after operation was significantly larger than that in the control group (P <0.05), and the ratio of intima area to medial area was smaller than that in the control group (P <0.05) The week was completed, while the control group did not complete until 4 weeks. Conclusion: Transfection of pcDNA3.0 / hVEGF165 gene can promote local vascular endothelialization, significantly reduce the degree of restenosis and intimal thickening.