生物可降解性基因释放血管内支架抑制小型猪肾动脉球囊扩张后c-myc基因表达及内膜增生的实验研究  

Gene-delievery biodegradable endovascular stent suppress c-myc gene expression and neointimal hyperplasia of balloon-injured porcine renal artery

作　　者：刘江涛[1] 张金山[1] 肖越勇[1] 李家开[1] 田锦林[1] 杨波[1] 

机构地区：[1]解放军总医院放射科,北京100853

出　　处：《中国医学影像技术》2007年第7期943-947,共5页Chinese Journal of Medical Imaging Technology

基　　金：国家自然科学基金资助项目(30370429)

摘　　要：目的研究释放ASODN基因片段的生物可降解血管内支架在抑制小型猪肾动脉球囊损伤后c-myc基因表达及内膜增生中的作用。方法将ASODN涂层BES与裸BES分别植入到16只实验小型猪球囊扩张后的双侧肾动脉内,分别在术后24 h、1周、4周及12周各处死4只动物;用Western Blot法进行c-myc基因蛋白表达分析;病理分析对两种支架不同时期的内膜厚度、内膜面积、管腔面积及PCNA染色增殖指数进行比较。结果ASODN涂层BES及裸BES置入段血管在损伤后12周内均表现出连续的内膜愈合与生长过程;支架置入后24 h,ASODN涂层BES置入段血管表达c-myc蛋白与健康肾动脉相似,均明显低于裸支架置入段血管,差异持续至术后4周;12周时,各组c-myc蛋白表达差异消失,裸BES、ASODN涂层BES置入段血管及健康肾动脉c-myc蛋白均呈微弱表达。除24 h外,ASODN涂层BES各期内膜增生程度均较裸BES弱,以支架周围明显,管腔面积均大于裸BES组,PCNA指数均小于裸BES组(P<0 .05)。结论ASODN涂层BES能有效抑制小型猪肾动脉球囊损伤后c-myc基因蛋白表达,损伤后12周内表现出对新生内膜增生较强的抑制作用,使用PLLA材料制作的BES是基因释放的良好载体。Objective To demonstrate the role of ASODN-coated biodegradable endovascular stent （BES） in surpressing c-myc gene expression and neointimal hyperplasia of balloon-injureud porcine renal artery. Methods ASODN-coated BES and naked BES were implanted into bilateral balloon-injrued renal artry of 16 pigs respectively and each 4 animals were sacrificed 24 hours, 1 week, 4 weeks and 12 weeks after BES implantation. The c-myc gene expression was analysed by Western Blot and neointimal thickness, neointimal area, lumen area and PCNA index of the vessels were analysed and compared between two groups. Results The neointima of vessels implanted with ASODN coated BES and naked BES showed continuous healing process. The c-myc expression of ASODN-coated BES was similar to that of healthy vessel, both of which were obviously lower than that of naked BES and the difference sustained to 4 weeks after injury. All specimens showed low expression of c-myc 12 weeks after injury. Neointimal hyperplasia and PCNA index, especially around the BES strut, of ASODN-coated BES was lower than that of naked BES and the lumen area was larger than that of the latter on all the time intervals after vessel injury except for 24 hours. Conclusion c-myc gene expression of balloon injured porcine reanal artery and succedental neointimal hyperplasia could be surpressesed by ASODN-delievery BES and PLLA stent was an optimal vehicle for antiproliferational gene reliesing.

关 键 词：生物可降解支架 基因治疗 内膜 再狭窄 

分 类 号：R815[医药卫生—放射医学]