摘要
目的:探讨32P液体球囊血管内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:取24只大耳白兔,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予9.1Gy、21.8Gy和33.4Gy32P液体球囊血管照射治疗,另一侧作为自身对照。术后5周行血管造影并取材进行光镜、电镜观察,增殖细胞核抗原(PCNA)、抑癌基因P53免疫组织化学染色,用计算机图像分析其组织形态学改变。结果:9.1Gy组未观察到明显的生物效应;21.8Gy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:32P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,其机制可能为抑制新生内膜形成和管腔面积丢失;促进平滑肌细胞凋亡以及抑制血管负性重塑。
Objective: To observe the dose-effect relation of endovascular brachytherapy with 32 P in preventing restenosis after angioplasty and to assess the possible mechanisms of irradiation therapy reducing restenosis. Methods: In 24 rabbits, the double iliac artery atherosclerotic stenosis model was set up. We performed angioplasty and 'P brachytherapy at one side randomly, the absorbed doses were 9. lGy, 21. 8Gy 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, and PCNA, P53 immunohistochemical techniques. We also measured morphological changes by computer analysis of photomicrographs. Results:There were no obvious changes in 9. 1Gy group. In 21. 8Gy group, the proliferation and migration of smooth muscle cells was significantly suppressed and the lumen areas did not decrease. However in 33. 4Gy group, the neointima was thick so as to make the cavity obvious stenosis, and the smooth muscle in media was shrinked and thinned, arterial thrombosis occurred in four vessels. Conclutions:Endovascular brachytherapy with 'P filled ballon catheter system could prevent restenosis after angioplasty. The mechanism may be due to reduce neointima formation and increase lumen size. It would be promoting apoptosis and improve the vascular remodeling.
基金
国家自然科学基金项目(30170233)