雷帕霉素-替罗非班复合药物涂层支架的血液及组织相容性  

In vivo blood compatibility and histocompatibility of rapamycin-tirofiban eluting stent

作　　者：刁繁荣[1] 吕安林[1] 张薇[1] 李军杰[1] 张荣庆[1] 苑媛[1] 胡小菁[1] 胡艳[1] 

机构地区：[1]解放军第四军医大学西京医院心内科,陕西省西安市710032

出　　处：《中国组织工程研究与临床康复》2007年第13期2411-2414,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

摘　　要：目的:观察雷帕霉素-替罗非班复合药物涂层支架置入后再狭窄、血栓、生化指标和重要器官组织病理学变化情况,评估其血液及组织相容性。方法:实验于2005-03/11在解放军第四军医大学实验外科实验室完成。以聚合高分子材料为药物载体,采用微喷法制备雷帕霉素支架及雷帕霉素-替罗非班复合药物涂层支架。实验分组:8只小型猪按随机数字表法分为两组,复合药物组和雷帕霉素组,每组4只。复合药物组应用雷帕霉素-替罗非班复合药物涂层支架,雷帕霉素组应用雷帕霉素支架。再狭窄模型采用国际公认的小型猪冠状动脉过度扩张再狭窄模型。每只猪于冠状动脉中成功置入上述支架各2枚。术后两组小型猪服用硫酸氯吡格雷75mg/d抗血小板治疗,雷帕霉素组服用3个月,复合药物组服用1个月。实验评估:①观察术后动物行为状态。②支架置入术前、术后2,7d,4,12周分析全血细胞计数、生化指标。③麻醉后处死动物,取出支架置入段血管,行组织病理学观察,计算管腔面积丢失率。管腔面积丢失率(%)=(支架围绕面积-管腔面积)/支架围绕面积×100%。④取肺、肝、肾组织及支架血管段供血的心室壁行组织学观察。结果:8只小型猪均进入结果分析。①术后动物行为学观察:两组术前、术中及术后3个月造影时,动物心率、血压、体质量的变化差异无显著性意义,术后也无明显行为异常及饮食、排尿便异常。②血细胞计数和生化检测结果:复合药物组、雷帕霉素组术后2d白细胞计数均高于术前[分别为(13.1±2.8)×109,(7.2±2.1)×109L-1;(12.5±3.3)×109,(6.3±2.2)×109L-1],差异有显著性意义(t=3.37,3.08,P<0.05);其余各时段两组外周全血红细胞、白细胞、血小板计数差异无显著性意义(P>0.05)。γ-血清谷丙转氨酶、谷氨酰转肽酶及肌酐、尿素氮未见明显改变(P>0.05)。③血管组织病理学检测:两组血管均AIM：To observe the thrombosis and restenosis, the changes of histopathological and biochemical indexes after rapamycin-tirofiban eluting stent （RTES） transplantation, and evaluate the blood compatibility and histocompatibility of RTES. METHODS： The experiment was accomplished in the Laboratory of Experimental Surgery, the Fourth Military Medical University of Chinese PLA between March and November in 2005. Grouping： Eight miniature pigs were randomly divided into experimental group （n =4） and control group （n =4）. Stents made with rapamycin-tirofiban and polymer were implanted into the coronary arteries of pigs in experimental group, while stents made with rapamycin and polymer were implanted in the control group. Coronary artery restenosis model was established with coronary over-stretch in swine, 2 stents for each swine. Clopidogrel of 75 mg/d was given for antiplatelet therapy, 3 months in control group and 1 month in experimental group. Evaluation： ①The behavior states of animal post-operatively. ②The whole blood cell counts and biochemical indexes before and 2 days, 7 days, 4 weeks, 12 weeks after stents were implanted.③All the animals were sacrificed, and the implanted vessels were selected to conduct histopathology observation and then calculate the lumen area losing rate. Losing rate of lumen area （%）= （Surrounding area of stents-lumen area）/surrounding area of stents × 100%. ④Lungs, livers, kidneys and the ventricular walls, which infused by the stents supported arteries, were also observed histologically. RESULTS： Eight miniature pigs were involved in the result analysis.①Animal ethology： Before, during and 3 months after the implantation, there was no significant difference in heart rate, blood pressure and body weight between two groups. Behavior, diet or urination was not influenced. ②Blood cell count and biochemistry： White blood cell number was increased in both groups 2 days post-operatively [（13.1±2..8）×10^9, （7.2±2.1）×10^9 L-l; （12.5±

关 键 词：支架 组织相容性 雷帕霉素 替罗非班 生物材料 

分 类 号：R318[医药卫生—生物医学工程]