本项目在模拟人类As和血管重建术后RS病理变化基础上，针对血管RS发生涉及多种基因异常表达，拟在血管重建术中，调控tPA，VEGF、PCNA和c-myc四个基因，试图阻止血管RS发生。从而深入探讨调控多基因在血管重建术中防治RS发生的作用，为血管RS基因治疗从实验研究向临床应用过渡奠定坚实基础，寻求人类征服动脉闭塞性疾病的有效途径。

Objective: To observe the effect of transfecting t-PA gene and PCNA-AODN together on angio-restenosis resulted from angioreconstruction, expecting to provide the experiment data for preventing restenosis resulted from angioreconstruction by multi-gene regulation. Methods: 1. First, colon human t-PA full-length genome and construct an recombinant eukaryotic expression plasmid containing tandem copies of t-PA genome. 2. The expression of t-PA in VEC transfected with pcDNA 3.1(t)/t-PA expression in VEC, and that had evident activity. 3. PCNA-AODN could inhibit the expression of PCNA mRNA and protein, the VSMC proliferation. 4.The model of angio-restenosis was constructed by operation injury to right external ilica arteries of rabbits. The rabbits was divided into 5 groups randomly. Group A pseudo-operation group; Group B model group; Group C pcDNA 3.1(t)/t-PA transfection; Group D PCNA-AODN transfection; Group E pcDNA 31(t)/t-PA and PCNA-AODN transfection group. Results: The transfection of t-PA and PCNA-AODN in local angio-wall could restrain thrombosis, excretion of PDGF and inhibit the proliferation, immigration and phenotypic change of VASM. Conclusions: The transfection of t-PA and PCNA-AODN in local angio-wall probably inhibits occurrence and development of angio-restenosis resulted from vascu

目的：观察在血管局部联合转染t-PA基因和PCNA-AODN对血管损伤再狭窄的影响，旨在为多基因联合调控防治血管重建术后再狭窄提供实验依据. 方法：1．首先克隆人t-PA基因并构建携带t-PA基因的真核表达重组质粒载体pcDNA3.1(t)/tPA.2．脂质体介导的pcDNA3.1(t)/t-PA质粒转染血管内皮细胞，测定t-PA的表达情况。3．PCNA寡核苷酸在脂质体介导下顺利进入VSMC。4．建立日本大白兔髂外动脉离断再吻合模型，随机分为五组，用微细针头在手术显微镜下，在两个断端不同位点内膜下注射生理盐水或载有t-PA、VEGF的基因质粒液. 结果：在血管局部联合转染t-PA基因和PCNA反义寡核苷酸能协同抑制血管重建术后引起的血栓形成，同时能抑制PDGF分泌和VSMC的增殖、迁移和表型变换。 结论：血管吻合口局部联合转染t-PA基因和PCNA反义寡核苷酸，能控制血管重建术后再狭窄的发生和发展