中国现代医学杂志2017,Vol.27Issue(17):13-18,6.DOI:10.3969/j.issn.1005-8982.2017.17.003
白蛋白纳米-基因涂层支架的研制及其抗血栓作用
Preparation of nanoparticle gene-coated stent and its antithrombotic effect
摘要
Abstract
Objective To prepare albumin nanoparticle tissue-type plasminogen activator (t-PA) gene-coated stent and observe its effect on prevention of in-stent thrombosis and intimal hyperplasia in rabbits. Methods Stainless steel stent was coated with the coating liquid which was prepared from the main components of vascular basement membrane (hyaluronic acid + type Ⅳ collagen + laminin + fibronectin). To prepare albumin nanoparticle t-PA gene-coated stent, the t-PA gene plasmid was packaged by albumin nanoparticles and then connected to the coating surface. A rabbit iliac artery intimal hyperplasia model was constructed with balloon catheter. The nanoparticle t-PA gene-coated stent was implanted into the iliac artery and t-PA gene was transfected with the aid of therapeutic ultrasound. The blood levels of prothrombin time, t-PA and D-dimer were measured before and 1, 2 and 4 weeks after operation. The vascular obstruction and in-stent thrombosis after stent implantation were observed by stereoscope and routine pathological examination. Morphometry was used to measure intimal thickness and area to determine intimal hyperplasia. The expressions of t-PA and proliferating cell nuclear antigen (PCNA) were detected by immunohistochemistry. Results The t-PA gene-coated stent was successfully prepared. The expression of t-PA protein in the implanted arteries was observed, accompanied by an increase in blood t-PA and D-dimer. There was no significant change in prothrombin time after implantation of the gene-coated stent. In-stent thrombosis and intimal hyperplasia were successfully suppressed. Conclusions The t-PA gene-coated stent can successfully inhibit in-stent thrombosis and intimal hyperplasia without affecting systemic coagulation of the rabbit. The complete synchronization of stenting and gene therapy provides the experimental basis for the development of nano-gene-coated stent and prevention of in-stent thrombosis.关键词
基因涂层支架/组织型纤溶酶原激活物/白蛋白纳米粒/血栓形成Key words
gene-coated stent/tissue-type plasminogen activator/albumin nanoparticle/thrombosis分类
医药卫生引用本文复制引用
何霞,季军,陈小玲,胡伟..白蛋白纳米-基因涂层支架的研制及其抗血栓作用[J].中国现代医学杂志,2017,27(17):13-18,6.基金项目
广东省医学科研基金(No:A2015529) (No:A2015529)