球囊导管转导血管内皮生长因子对局部血管内皮细胞生长的影响(英文)

Effects of vascular endothelial growth factor transduction through a Foley’s catheter on local vascular endothelial cell growth

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 vascular endothelial regeneration, inhibit thrombosis, and attenuate neonatal intimal thickness and luminal stenosis degree. OBJECTIVE： The present study established atherosclerosis models in rabbits and observed the effects of local transfection of VEGF gene on restenosis after angioplasty. DESIGN, TIME AND SETTING： A randomized controlled animal experiment was performed at the Laboratory of Microorganism, Tongji Medical College, Huazhong University of Science and Technology between November 2004 and December 2006. MATERIALS： Rabbits were daily raised with high-fat diet to create atherosclerosis models. Twenty successful rabbit models were randomly and evenly divided into a control group and a gene treatment group. METHODS： The pcNDA 3.0 recombinant human VEGF165 （hVEGF165） was transferred to the ventral aorta through the use of Foley＇s catheters, and the pcDNA3.0 was transferred in the controls. MAIN OUTCOME MEASURES： At 1, 2, and 4 weeks after surgery, luminal area of left renal artery opening was measured by MRI. At 2 and 4 weeks after surgery, the ratio for intimal to medial area was obtained through the use of HMIAS-2000 high definition color medical image analysis software. Simultaneously, vascular endothelial cell regeneration was observed by immunohistochemistry of factor Ⅷ related antigen. RESULTS： The pcDNA3.0/hVEGFI65 could be successfully transferred through the use of Foley＇s catheters. At 2 and 4 weeks after surgery, luminal area was larger in the gene treatment group than in the control group （P 〈 0.01）; simultaneously, the ratio of intimal to medial area was significantly smaller in the gene treatment group than in the control group （P 〈 0.05）. In the gene treatment group, expanded vascular endothelial cell regeneration was accomplished at 2 weeks after surgery, while in the control group, it took 4 weeks. CONCLUSION： pcDNA3.0/hVEGF165 gene transduction can promote local vascular endothelialization and apparently attenuate restenosis degree and intiaml thickening.