三氧化二砷洗脱支架防治兔血管损伤后再狭窄的实验研究  

Arsenic trioxide eluting stents to prevent restenosis of injured iliac arteries in rabbits

作　　者：杨巍[1] 葛均波[2] 刘红玲[1] 安毅[3] 刘学波[2] 田野[1] 曲秀芬[1] 李为民[1] 黄永麟[1] 

机构地区：[1]哈尔滨医科大学附属第一医院,150001 [2]上海复旦大学中山医院心血管病研究所 [3]青岛大学医学院附属医院心内科

出　　处：《中华心血管病杂志》2006年第1期14-18,共5页Chinese Journal of Cardiology

基　　金：国家自然科学基金资助项目(30170368);哈尔滨市科委基金资助项目(3152)

摘　　要：目的冠状动脉支架内再狭窄主要是由血管损伤后内膜增生引起,研究三氧化二砷(As2O3)多聚左旋乳糖酸(PLLA)涂层的药物洗脱支架在兔的损伤髂动脉内抑制内膜增生防治再狭窄的疗效、机制及As2O3释放的药物代谢动力学。方法45只雄性新西兰白兔,随机分三组,每组15只,分别将裸支架、PLLA涂层支架、As2O3洗脱支架置入兔髂动脉的近端,饲养28d后处死,组织病理学检测内膜厚度,TUNEL法测细胞凋亡。在体药代动力学研究:雄性新西兰白兔48只,按支架置入后饲养时间(2h、1d、3d、7d、14d、28d)分为6组,每组8只,检测血浆中及支架处组织中的As2O3浓度。结果As2O3洗脱支架释放As2O3达28d,第一天支架处组织中的As2O3浓度约是血浆中的55000倍,14d约为22000倍。As2O3洗脱支架较PLLA支架和裸支架分别减少内膜增生51%、31%。As2O3洗脱支架组较PLLA支架组和裸支架组血管平滑肌细胞凋亡面积明显增加(21·0±3·3比6·2±1·9,5·3±2·1)。结论As2O3洗脱支架在局部血管处释放As2O3达28d,在兔的髂动脉可有效抑制由支架和球囊损伤导致的兔血管内膜增生,其机制之一是促进平滑肌细胞凋亡。Objective To assess the efficiency of eluting stent coated with arsenic trioxide （As2O3 ） suspended in poly-L-lactic acid （PLLA） to prevent in-stent restenosis in rabbits. Methods Forty-five male New Zealand white rabbits were assigned to three groups （n=15 for each group） at random： uncoated stents, stents coated with PLLA or stents coated with As2O3 in PLLA. Animals were euthanized 28 days after stent implantation into the iliac arteries of rabbits. Neointimal thicknesses and apoptosis of vascular smooth muscle cell （VSMC） were measured. Stents coated with As2O3 in PLLA were implanted in another 48 male New Zealand white rabbits, As2O3 concentrations in serum and arterial tissue at implantation site were measured at 2 h and 1, 3, 7, 14, 28 days after As2O3 eluting stent implantation （ n = 8 for each time point）. Results Neointimal hyperplasia was significantly reduced 51% and 31% and apoptosis significantly increased （21.0 ± 3.3 ; 6. 2 ± 1.9^ ＊ ; 5. 3 ± 2. 1^＊ , ^＊P 〈 0. 01 vs. As2O3 eluting stent ） with As2O3 eluting stent, versus PLLA-coated stents and uncoated stents. As2O3 concentrations in arterial tissue at implantation site were 18.6 ± 9.1 （ng/mg） at 1 day and 0.3 ± 0.1 （ng/mg） at 28 days after stent implantation. Conclusions As2O3 coated stents released As2O3 to local tissue for at least 28 days, suppressed neointimal hyperplasia in rabbit iliac arteries and increased local VSMC apoptosis might be one of the mechanisms for inhibiting restenosis by As2O3 coated stents.

关 键 词：冠状动脉再狭窄 支架 三氧化二砷 

分 类 号：R541.4[医药卫生—心血管疾病] R-332[医药卫生—内科学]