聚氨酯植入装置用于血管内局部定位基因治疗的实验研究
首发时间:2006-03-02
摘要:目的 利用可植入体内的经过修饰的功能化聚氨酯构建2种血管内植入装置,分别植入猪主动脉和羊肺中进行基因转染实验,研究其作为基因运载平台的可行性。方法 将涂覆胶原的聚氨酯膜通过抗体免疫偶联编码绿色荧光蛋白的腺病毒(AdGFP)制备成聚氨酯-胶原膜埋植钮装置并植入猪主动脉中,7天后取出埋植钮及其周围组织进行切片、荧光显微镜检测及PCR分析,用以评价AdGFP的转染情况及分布;将抗腺病毒抗体直接通过共价连接在带有硫醇化烷基的功能化聚氨酯膜上实现与AdGFP的免疫偶联,制备成聚氨酯人工瓣膜并植入羊肺中,7天后取出肺部小叶及其周围组织进行荧光显微镜检测及PCR分析,用以评价AdGFP的转染情况及分布。结果 在猪体内实验中,植入体表面的新生内膜细胞基因转染率为14.3±2.5%;在羊体内实验中,聚氨酯瓣膜小叶上的细胞有25.1±5.7%被转染。PCR研究表明血液或末端组织中都没有检测到GFP DNA。结论 研究表明这两种血管内聚氨酯基因载运系统能够作为靶向高效载运腺病毒的载体,用于心血管疾病的基因治疗。
关键词: 功能化聚氨酯 埋植钮 人工瓣膜 基因治疗
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Modified Polyurethane Devices for Endovascular Gene Delivery System
Abstract:Objective To explore the feasibility of utilizing two implantable devices made from modified polyurethane films with antibody tethered AdGFP as gene delivery platforms. Methods Intra-aortic button implants of collagen–coated polyurethane films with antibody tethered AdGFP were sutured into the infrarenal aorta of adult pigs and pulmonary valve leaflet in juvenile sheep was replaced by polyurethane pulmonary valve cusp replacement with antibody-tethered AdGFP. After 7 days, the buttons, prosthetic leaflets and their surrounding tissues were explanted and evaluated for biocompatibility and AdGFP-mediated gene transfer by fluorescent microscopy and PCR analyses. Results In vivo analysis of gene transfer from collagen-coated polyurethane films in pig infrarenal aorta implants, one week explants of the collagen-coated polyurethane films demonstrated14.3±2.5% of neointimal cells on the surface of the implant. In sheep pulmonary valve leaflet replacement studies, polyurethane films with antibody tethered AdGFP vector demonstrated 25.1±5.7% of cells attached to polyurethane valve leaflets were transduced in 1 week. PCR analyses showed that GFP DNA was not detectable in blood or distal tissues. Conclusions It is concluded that site-specific intravascular delivery of adenoviral vectors for gene therapy can be achieved with these two kinds polyurethane implants utilizing the antivector antibody tethering mechanism.
Keywords: modified polyurethane button implant prosthetic leaflet gene therapy
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No.5468176941141267****
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聚氨酯植入装置用于血管内局部定位基因治疗的实验研究
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