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壳聚糖/肝素西罗莫司药物洗脱支架对猪冠状动脉血栓形成及早期快速内皮化的作用
郜俊清,金惠根,严鹏勇,张文全,武前福,刘宗军*
0
(上海市普陀区中心医院心内科,上海 200062
*通信作者)
摘要:
目的 将壳聚糖/肝素涂层膜应用于西罗莫司药物洗脱支架(DES),明确壳聚糖/肝素西罗莫司DES对猪冠状动脉血栓形成及早期快速内皮化的作用。 方法 将壳聚糖/肝素层层自组装涂层膜应用于西罗莫司DES,并采用非对称涂抹方式使支架血液面为壳聚糖/肝素涂层,而支架血管壁面为聚乳酸(PLA)-西罗莫司。实验分为裸金属支架(BMS)组、壳聚糖/肝素支架组、西罗莫司DES组和壳聚糖/肝素西罗莫司DES组,采用动静脉分流模型和高负荷血栓模型验证壳聚糖/肝素西罗莫司DES的抗血栓作用;采用为期1周的猪冠状动脉球囊损伤动物实验观察壳聚糖/肝素西罗莫司DES对早期内皮化的作用。 结果 在动静脉分流模型中,壳聚糖/肝素西罗莫司DES和壳聚糖/肝素支架表面未形成血栓,而BMS和西罗莫司DES表面覆满血栓;在高负荷血栓模型中,壳聚糖/肝素西罗莫司DES和壳聚糖/肝素支架在6 h内未出现支架内血栓,而BMS和西罗莫司DES分别在(59.0±8.5) min和(67.0±7.8) min时出现支架血栓,差异有统计学意义(P<0.01)。在猪冠状动脉球囊损伤动物模型中,壳聚糖/肝素西罗莫司DES和壳聚糖/肝素支架置入7 d后内皮覆盖率分别为(82.7±16.4)%和(80.7±14.1)%,高于 BMS和西罗莫司DES\[分别为(64.3±11.0)%和(59.8±8.4)%,P<0.01\]。 结论 壳聚糖/肝素涂层西罗莫司DES具有较好的抗血栓作用,且能够在早期促进支架内皮化。
关键词:  药物洗脱支架  层层自组装  壳聚糖  肝素  内皮化  血栓形成
DOI:
投稿时间:2013-05-07修订日期:2013-07-28
基金项目:上海市医学重点专科建设项目(05-Ⅱ026),上海市普陀区科委基金.
Chitosan/heparin sirolimus drug-eluting stent system improves anticoagulation and promotes early re-endothelialization in porcine coronary artery
GAO Jun-qing,JIN Hui-gen,YAN Peng-yong,ZHANG Wen-quan,WU Qian-fu,LIU Zong-jun*
(Department of Cardiology, Central Hospital of Shanghai Putuo District, Shanghai 200062, China
*Corresponding author.)
Abstract:
Objective To construct a sirolimus loaded drug-eluting stent (DES) using chitosan/heparin coating membrane and to explore its effect on anticoagulation and early re-endothelialization in porcine coronary artery.Methods Chitosan/heparin layer-by-layer self-assembly coating was applied to sirolimus DES, and the asymmetric applicator was used to allow for the stent blood surface to be chitosan/heparin coated and the stent vascular surface to be polylactic acid (PLA)-sirolimus. The experiment was divided into bare metal stent (BMS) group, chitosan/heparin stent group, sirolimus DES group and chitosan/heparin sirolimus DES group.The anticoagulation effect of chitosan/heparin sirolimus DES was tested by arteriovenous shunt model and high load thrombosis model. The effect of chitosan/heparin sirolimus DES on early re-endothelialization was tested by 1-week long balloon injury to porcine coronary artery. Results No thrombus was found on the surfaces of chitosan/heparin sirolimus DES and chitosan/heparin stent in the arteriovenous shunt model, while the surfaces of BMS and sirolimus DES were covered with thrombus. No stent thrombosis was found in the high load thrombosis model test of chitosan/heparin sirolimus DES and chitosan/heparin stent within 6 hours, and stent thrombosis was found in BMS at (59.0±8.5) min and in sirolimus DES at (67.0±7.8) min (P<0.01). The early re-endothelialization test showed endothelial coverage rates of chitosan/heparin sirolimus DES and chitosan/heparin stent after 7 d implantation were (82.7±16.4)% and (80.7±14.1)%, significantly higher than those of BMS and sirolimus DES (\[64.3±11\]% and \[59.8±8.4\]%, respectively; P<0.01).Conclusion Chitosan/heparin-coated-sirolimus DES has satisfactory anticoagulation property and it can accelerate early re-endothelialization.
Key words:  drug-eluting stents  layer-by-layer self-assembly  chitosan  heparin  endothelialization  thrombosis