载基因洗脱支架防治再狭窄的研究进展

Progress of the Prevention of Restenosis with Gene Eluting Stents

药物洗脱支架(DES)在冠状动脉疾病的治疗中起到巨大作用,不但能机械支撑血管狭窄区,而且可以通过持续释放药物显著降低病灶处再狭窄率。然而,长期临床研究表明,载药DES在后期有引发血栓的风险。在DES表面载入基因药物,通过表面涂层输送系统局部缓慢释放治疗基因,能针对引起再狭窄的细胞过程进行修改。选择合适的治疗基因,可以抑制内膜增生,促进再内皮化,提高洗脱支架的有效性和安全性,是非常有前途的抗再狭窄方法。同时,良好的涂层材料不仅改善了支架表面的生物相容性,更能通过不同的基因药物输送系统有效控制治疗基因的释放速率。本文首先介绍了一部分针对再狭窄的治疗基因,在此基础上,综合阐述了基因缓释系统中使用的材料和技术,分析提炼了基因缓释系统的释放机理,举例分析了载基因洗脱支架的研究进展,并展望了该领域的发展前景。

Drug-eluting stents（DES） have provided a breakthrough in the treatment of coronary artery disease（CAD）, it not only supports narrow vessel and keeps vessel open by mechanical force, but also obviously reduce the rate of restenosis by the sustained release of drug on the targeted sites. However, long term clinical studies demonstrated the high risk of late thrombosis following DES use in the late stage. Surface modification of DES with coating biomaterials combined with gene can modify cellular processes that give rise to restenosis through the sustained release gene delivery system. Some suitable therapeutic genes can improve the efficacy and safety of eluting stents by inhibiting neointimal proliferation and promoting re-endothelialization, which would be a promising method of prevention of restenosis. Meanwhile, coating materials with great property improve the biocompatibility of stents surface, and even effectively control the releasing rate of therapeutic genes via different gene delivery system. In this paper, the therapeutic gene was classified by the different strategies of anti-restenosis; the widely used materials and technology for DES coating design were introduced; in addition, the basic mechanism of gene delivery from biomaterials was discussed; some applications of stents were reviewed for their effective treatment on the animal models; and finally the future perspective was provided for gene therapy in DESs.