新型肝素化聚氨酯涂层三氧化二砷洗脱支架的初步研究  

Preliminary study on arsenic trioxide eluting stent with a heparin-immobilized polyurethane coating

作　　者：陆跃[1] 沈雳[1] 龚飞荣[1] 饶炬[1] 陈建定[1] 田文杰[2] 吴轶喆[2] 张峰[2] 杨巍[2] 葛均波[2] 

机构地区：[1]华东理工大学材料科学与工程学院,超细材料制备与应用教育部重点实验室,上海200237 [2]复旦大学附属中山医院心内科,上海市心血管病研究所

出　　处：《上海医学》2012年第3期185-188,I0001,共5页Shanghai Medical Journal

基　　金：国家863项目(2007AA02Z450);国家自然基金项目(81101133);上海市科学技术委员会课题(11441900300)资助

摘　　要：目的研究新型三氧化二砷洗脱支架(AES)的涂层材料的生物相容性及其药物释放的特征及初步功效。方法以肝素化聚氨酯为药物支架涂层材料,三氧化二砷(As2O3)为药物,成功制备新型AES,研究其在(37±0.5)℃、体外磷酸盐缓冲溶液(PBS,pH值=7.4)中的释放规律。在体内比较AES与金属裸支架(BMS)植入4周时的相关组织反应及血管内膜增生的情况,观察支架表面的内皮化进程及内皮功能恢复情况。结果支架所载药物在1周内全部释放。支架植入1周后,AES植入处的冠状动脉平滑肌细胞凋亡率为(62.6±9.6)%,显著高于BMS及单聚合物涂层支架(PCS)植入处的(18.1±3.3)%及(21.2±5.3)%(P值均<0.05)。AES植入处血管的管腔面积较BMS及PCS植入处显著增加(P值均<0.05),而内膜面积、支架内再狭窄(ISR)发生率及内膜厚度均显著减少(P值均<0.05)。支架植入4周后,BMS及AES植入处表面均内皮化完全。以60mg/mL的速度注入乙酰胆碱,BMS、PCS、AES植入处血管的平均收缩率分别为(21.7±4.5)%、(20.4±3.7)%、(23.3±4.2)%,3种支架间的差异无统计学意义(P>0.05)。结论新型聚氨酯涂层的AES具有良好的生物相容性,其药物释放在动物冠状动脉支架植入模型中可有效抑制内膜增生,并具有较好的内皮覆盖性能。该支架的深入研究及优化有望为临床提供一种在减少ISR发生的同时,可降低不良事件发生率的新型内皮友好型支架。Objective To evaluate the biocompatibility,drug release and preliminary efficacy of arsenic trioxide(As2O3) eluting stent(AES) with a new heparin-immobilized polyurethane coating.Methods A new AES was successfully developed with heparin-immobilized polyurethane as coating material and As2O3 as the drug.Drug release was measured in phosphate buffered solution(PBS,pH=7.4) at(37±0.5) ℃.In a porcine stent implantation model,the thicknesses and apoptosis of vascular smooth muscle cells(VSMC) as well as stent surface endothelialization and endothelial function were investigated between AES and bare metal stents 4 weeks after stent implantation.Results In vitro As2O3 release study indicated that the drug was totally released within 7 days.The apoptosis rate of VSMC in the coronary arteries with AES was significantly higher than those in BMS and polymer coated stent(PCS) one week after stent implantation([62.6±9.6]%,[18.1±3.3]%,and [21.2±5.3]%,P<0.05).Compared with BMS and PCS,the area of lumen of blood vessel in the coronary arteries with AES was significantly increased,but the area and thickness of endomembrane and in-stent restenosis was significantly decreased(P<0.05).Complete endothelialization on the surface of BMS and AES was achieved 4 weeks after stent implantation.The diameter changes in response to the Ach infusion(60 mg/mL) in sites distal to the stents between BMS,PCS and AES had no significant differences([21.7±4.5]%,[20.4±3.7]% and [20.4±3.7]%,P>0.05).Conclusion The new AES has good biocompatibility and may be a promising endothelial-friendly drug eluting stent.It can effectively inhibit restenosis and reduce adverse events such as late stent thrombosis in porcine model.

关 键 词：肝素化聚氨酯 三氧化二砷支架 涂层 再狭窄 内皮化 

分 类 号：R318.08[医药卫生—生物医学工程]