纳米粒子介导Egr-1 DNA酶转染抑制移植静脉内膜增生

背景：应用基因防治移植血管狭窄、闭塞现已被普遍公认,但如何增加其转染效率现已成为焦点及热点问题。目的：观察以纳米粒子为载体的外源性Egr-1 DNA酶局部转染对移植静脉内膜增生的影响。方法：构建Egr-1DNA酶,应用聚乳酸聚乙醇酸共聚物和聚乙烯醇包载Egr-1 DNA酶,制备纳米级粒子混合物。建立自体静脉移植模型210只,随机分成3组,转基因组转染以纳米粒子为载体的Egr-1 DNA酶,空载体组单纯转染纳米粒子包载的空载体,对照组不予特殊处理。结果与结论：转基因组内膜中Egr-1基因的mRNA及蛋白产物表达较其他两组明显减少（P〈0.05）;在术后7,14,28d,转基因组内膜增生厚度较其他两组明显减少（P〈0.01）;转基因组血管平滑肌细胞凋亡百分比较其他两组明显增高（P〈0.05）。结果表明Egr-1DNA酶的表达能有效抑制自体移植静脉内膜的增生及促进血管平滑肌细胞凋亡。

Transfection of early growth response gene-1 DNA enzyme mediated by nanoparticles inhibits vein graft intimal hyperplasia

BACKGROUND： The method of gene has been admitted to prevent stenosis and occlusion of grafted vascular. But it is a hot spot of how to increase gene transfection efficiency. OBJECTIVE： To study the effect of partial transfection of exogenous early growth response gene-1 DNA enzyme （Egr-1 DNA enzyme, EDRz） mediated by nanoparticles （NP） on the intimal hyperplasia （IH） in grafted vein. METHODS： The EDRz was constructed. Nanoparticle EDRz complex was prepared with polylactic/poly glycolic acid （PLGA） and polyvinyl alcohol （PVA）. Autogenously vein graft model was established, and the 210 rats were divided into three groups randomly： （1） EDRz group, EDRz mediated by NP was transfected into the veins before anastomosis. （2） Empty vector group, the vein was transfected by empty vector mediated by NP. （3） Control group, no transfection. RESULTS AND CONCLUSION： In EDRz group, the expression of mRNA and protein of Egr-1 gene in intimal was significant decreased than that in other two groups （P〈0.05） and at the 7th, 14th and 28th days, the thickness of intimal hyperplasia was decreased than that in other two groups （P 0.01）, the apoptotic percentage of vascular smooth muscle cells in EDRz group was significant increased than that in other two groups （P〈0.05）. EDRz expression can prevent intimal hyperplasia and promote apoptosis of vascular smooth muscle cells after autogenous vein grafting.