中文摘要：

目的探讨国产外周动脉雷帕霉素-肝素洗脱支架（SHES）的物理性能，生物相容性和体内外药代动力学特性，以及其对再狭窄的抑制作用。方法将聚丙交酯乙交酯（PLGA）与肝素混合成溶液，雾化喷射于覆载雷帕霉素聚合物涂层的镍钛合金支架表面，再形成载肝素聚合物涂层而制成SHES；继而，对其进行物理性能和降解特性检测以及血液相容性试验和体外药代动力学研究。将14枚研制成的SHES、8枚雷帕霉素洗脱支架（SES）和8枚裸支架分别置入15只犬外周动脉；在严格抗凝情况下，于支架放置术后30、60和240d分别对7只、7只和1只犬进行造影观察，其后15只犬全部处死作下列观测：支架顺应性、径向力和可视性等，支架段和参考节段内直径，以及其直径晚期丢失值，血栓形成，支架和参考节段再狭窄率等。结果SHES表面质量良好，与支架有良好的结合力。血液相容性实验结果表明：载药涂层表面，黏附仅见少量血小板，且无变形和明显聚集，而致其凝血时间延长。凝血因子被激活的程度低；降解实验及体外药物释放结果表明：雷帕霉素释放时间可持续约3个月，肝素全部释放时间约50d。成功置入15只犬30枚支架，位置良好，未发生移位、脱落或不张等。SHES支架具有良好的柔顺性，于X线下显示清晰；当其释放后雷帕霉素即刻浓度为1．79～2．22ng／ml，7d达0．4ng／ml，可持续释放约3个月。7只犬术后30d造影显示：全部支架管腔通畅，无血栓形成或管腔狭窄发生；另7只犬术后60d造影显示：2枚SES血栓性闭塞，1枚SHES支架和3枚裸支架不同程度狭窄，另1枚SHES近端的血管轻度内陷；SHES与SES、裸支架支架段直径间以及支架段直径晚期丢失值间均存在差异，且具有统计学意义。双侧髂动脉置入SHES的1只犬术后240d造影显示：双侧髂动脉SHES通畅，未见狭窄或血栓?

英文摘要：

Objective To evaluate the physical properties, biocompatibility, and pharmacokinetics of the China-made sirolimus-heparin eluting stent （SHES） as well as its inhibition effect on the in-stent restenosis in vitro and in vivo. Methods Polylactide coglycotide （PLGA）-heparin complex was sprayed to the surface of sirolimus-coated nitinol stent to make the sirolimus-heparin eluting stentt （SHES）. The physical and degrading efiiciency, blood compatibility, and pharmacokinetics of this stent were studied in vitro. Fifteen dogs were implanted with SHES ＋ bare-metal stent （BMS） into the bilateral iliac arteries （ n = 4 ）, sirolimus-eluting stent （SES） ＋ BMS into the bilateral iliac arteries （n = 4）, SHES ＋ SES into the bilateral iliac arteries （n = 4）, and with 2 SHESs into the bilateral iliac arteries （ n = 2）, and 2 SHESs into the abdominal aorta （n = 1 ）. Based on the condition of strict anticoagulation, 30, 60, and 240 days after the implantation angiography of the peripheral arteries where the stents were placed was performed in 7, 7, and 1 dog respectively. Then all of the dogs were killed. The compliance, radial force, and visibility of stentt,in-stent thrombosis, in-stent diameter, reference segment diameter, late loss of diameter, and restenosis rate were observed. Results The SHES had even surface coating, and good compliance and radial extension. Blood compatibility test showed only few platelets adhered to the stent surface without deformity or obvious aggregation, and the clotting time was prolonged because of the blood coagulation factors to be activated in a low level. Degrading test and pharmacokinetics in vitro showed that sirolimus could be continuously released in a period of 3 months and heparin in a period of 50 day . The whole 30 stents were successfully implanted into the dog peripheral arteries without complication. The SHES showed satisfactory compliance and good visibility , and its blood concentration of sirolimus was 1. 79 - 2. 22 ng/ml immediately a