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

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：基因治疗缌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。

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

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 DcNDA 3.0 recombinant human VEGF165(hVEGF 165)was trimsferred to the ventral aorta through the use of Foley's catheters.and the pcDNA3.0 was transfefred 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/hVEGF 165 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/hVEGF 165 gene transduction can promote local vascular endotllelialization and apparently attenuate restenosis degree and intiaml thickening.