雷帕霉素洗脱支架抑制猪颈动脉成形术后近期再狭窄的实验研究  

Experimental study of sirolimus-eluting stent on prevention of early restenosis of porcine carotid artery after angioplasty

作　　者：梁海兵[1] 章希炜[1] 董剑[1] 邹君杰[1] 苗毅[1] 

机构地区：[1]南京医科大学第一附属医院普外科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2008年第8期990-993,1014,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省人事厅2005年度留学人员科技活动项目

摘　　要：目的:研究自膨式雷帕霉素洗脱支架防治猪颈动脉血管成形术后近期再狭窄的有效性安全性,及其作用机制。方法:国产小型猪6只,分别行双侧颈总动脉球囊扩张损伤后,随机分为对照组(裸支架组)和实验组(雷帕霉素洗脱支架组),各置入6枚。术后4周重复动脉造影后处死动物。取出支架段血管,测算支架处血管管腔面积、新生内膜厚度与面积及管腔狭窄百分比以评价内膜增生程度。应用TUNEL法检测新生内膜细胞凋亡指数(apoptotic index,AI),免疫组化检测血管平滑肌细胞中增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、Bcl-2、Bax表达水平。结果:雷帕霉素洗脱支架组支架内管腔面积大于裸支架组(P<0.05);新生内膜面积小于裸支架组(P<0.05);新生内膜厚度小于裸支架组(P<0.05);细胞凋亡多于裸支架组(P<0.05);PCNA阳性细胞及Bcl-2表达低于裸支架组(P<0.05);Bax表达高于裸支架组(P<0.05)。结论:雷帕霉素洗脱支架能抑制新生内膜形成,在支架植入后4周能预防猪颈动脉血管成形术后近期再狭窄的形成。可能通过上调Bax,下调Bcl-2的表达,从而抑制血管平滑肌细胞增殖发挥作用。Objective：To assess the efficacy, safety and mechanism of self-expanding sirolimus-eluting stent implanted in porcine carotid artery for preventing from early restenosis after angioplasty. Methods：After angioplasty on the dual common carotid arteries by ballon overstretch,6 sirolimus-eluting stents and 6 bare metal stents were implanted in 12 injured carotid arteries of 6 chinese minipigs at random, respectively. Four weeks later,after angiography 6 chinese minipigs were executed. Lumen area,neointimal thickness and area of injured arteries segment were measured by computer image analysis technique. The arteries segment were removed for measurement of the apoptotic index by TUNEL assay and the expression of proliferating cell nuclear antigen（PCNA）, Bcl-2 and Bax proteins by immunohistochemistry. Results： Compared with the bare metal stent group,the lumen area of sirolimus group was significantly greater while the neointimal thickness and area was significantly smaller（P 〈 0.05）. PCNA and Bcl-2 expression was significantly decreased in sirolimus-eluting stent group （P 〈 0.05）, while apoptotic index and Bax expression was significantly increased （P 〈 0.05）. Conclusion：Sirolimus-eluting stent can effectively inhibit neointimal formation to prevent early restenosis in porcine common carotid artery 4 weeks after implantation, with the possible mechanism of upregulating the expression of Bax, downregulating the expression of Bcl-2 and inhibiting vascular smooth muscle cell proliferation.

关 键 词：再狭窄 药物洗脱支架 雷帕霉素 增殖细胞核抗原 Bcl-2 Bax 

分 类 号：R543.4[医药卫生—心血管疾病]