放射治疗对兔髂动脉粥样硬化狭窄成形术后再狭窄的影响  

Effect of Radiotherapy on Restenosis after Angioplasty in Rabbits Iliac Artery Atherosclerosis

作　　者：刘寅[1] 高静[1] 徐美林[2] 苑淑渝[3] 徐乃勋[4] 赵鸿铭[5] 刘国庆[5] 赵炳让 

机构地区：[1]天津市胸科医院心内科 [2]天津市胸科医院病理科 [3]中国医学科学院放射医学研究所,300051 [4]天津市胸科医院放射科 [5]天津市胸科医院心血管病研究所

出　　处：《中国分子心脏病学杂志》2004年第2期108-113,共6页Molecular Cardiology of China

基　　金：国家自然科学基金项目资助 (编号 30 1 70 2 33)

摘　　要：目的 :探讨32 P液体球囊血管近距离照射预防血管成形术后再狭窄的量效关系及其抑制再狭窄发生的可能机制。方法 :2 4只大耳白兔 ,采用髂动脉内膜损伤加高脂饲养 6周 ,建立兔双侧髂动脉粥样硬化狭窄模型 ,随机选择一侧髂动脉血管成形术并分别给与 9 1Gy、 2 1 8Gy和 33 4Gy32 P液体球囊血管照射治疗 ,另一侧髂动脉灌注造影剂 ,作为自身对照。术后 5周行血管造影并取材进行光镜观察、电镜观察、核因子 κB (NF κB)、胰岛素样生长因子 1 (IGF 1 )免疫组织化学染色 ,用计算机图像分析测量新生内膜面积、中膜面积、管腔面积及免疫组化染色阳性面积百分比。结果 :对照组血管段内膜明显增生 ,管腔明显狭窄 ;9 1Gy组未观察到明显的生物效应 ;2 1 8Gy组血管壁平滑肌细胞增殖和迁移明显受抑 ,管腔面积无明显丢失 ;33 4Gy组管腔重度狭窄 ,内膜严重增厚 ,中膜平滑肌明显萎缩变薄 ,4例血管腔内血栓形成。结论 :32 P液体球囊在一定的吸收剂量范围内确可安全有效地防止血管成形术后再狭窄形成 ,其机制可能为是抑制新生内膜形成和管腔面积丢失 ;抑制NF κB及其靶基因的活化 ,从而抑制血管平滑肌细胞的增殖、迁移 。Objective To observe the dose-effect relation of endovascular brachytherapy with ^32P preventing restenosis after angioplasty and to assess the possible mechanisms of irradiation therapy reducing restenosis. Methods After ballon endothelial injury of iliac arteries and six weeks cholesterol-fed in 24 rabbits, the double iliac artery atherosclerotic stenosis model was set up. We procedured angioplasty and ^32P brachytherapy at one side randomly, the absorbed doses were 9.1Gy, 21.SGy and 33.4Gy, respectively, the other side non-radiative therapy was served as self-controled. After five weeks, the iliac artery angiography was performed, pathological sections of iliac arteries were observed with light-microscope, transmisson electron nuclear factor-κB （NF-κB）, insulin like growth- 1 （IGF-1）was stained using immunohistochemical techniques. We also measured the neointima areas, lumen areas, media areas and the percentage of NF-κB, IGF-1 positive areas by computer analysis of photomicrographs. Results Strong neointimal proliferation and strait lumen were observed in the control group. There weren＇t obvious changes in 9. 1Gy group; In 21.8Gy group, the proliferation and migration of smooth muscle ceils was significantly suppressed and the lumen areas did not decrease; however the neointima thicked to make the cavity obvious stenosis, and the smooth in media was shrinked and thinned in 33. 4Gy group, four vessels occurred arterial thrombosis. Conclusions Endovascular brachytherapy with 32 p filled ballon catheter system could prevent restenosis after angioplasty, the mechanism may be due to reduce neointima formation and increase lumen size; inhibit the activation of NF-κB and its target gene, which reduce the proliferation and migration of smooth muscle cells; increase apoptosis and improve the vascular remodeling.

关 键 词：血管内近距离照射 血管成形术 再狭窄 剂量 核因子-ΚB 

分 类 号：R543[医药卫生—心血管疾病]