内放射对兔颈动脉术后中膜平滑肌细胞增殖与凋亡的影响

Effects of Endovascular Radiation on the Proliferation and Apoptosis of Vascular Medial Smooth Muscle Cells in Rabbits after Carotid Endarterectomy

目的 通过血管内放射防治颈动脉内膜剥脱术 (CEA)后再狭窄 ,动态观察其对中膜平滑肌细胞(SMC)凋亡和增殖的影响 ,并初步探讨其防治再狭窄的可能机理。方法 4 0只兔行CEA后 ,随机分为 4组 ,分别给予 0Gy、10Gy、2 0Gy及 4 0Gy放射剂量的3 2 P ,于术后 3d、7d、14d、2 8d及 5 6d分别处死动物 ,取出血管标本进行病理组织学分析。结果 术后除 3d及 7d外 ,对照组发生明显内、中膜增生及管腔狭窄 ,而内放射组可见内、中膜增生明显受抑制 ,管腔面积缩小显著减轻 (P<0 .0 5 )。SMC凋亡率和细胞增殖核抗原 (PCNA)阳性细胞均于术后 3d增加 ,7d时达高峰 ,治疗组与对照组比较差异有显著性意义 (P<0 .0 1) ;2 0Gy和 4 0Gy的作用明显强于 10Gy组 (P<0 .0 1)。结论 内放射治疗可能是通过抑制SMC增殖、迁移 ,诱导SMC凋亡 ,防治再狭窄 ,并且随剂量呈递增效应 ;球囊损伤后早期以细胞增生和凋亡为主要表现 ,晚期表现为内。

Objective To observe the effects of endovascular radiation (ER) on the proliferation and apoptosis of medial smooth muscle cells (SMC) and to discuss the possible mechanisms of radiation in the prevention of vascular restenosis (RS) in rabbits after carotid endarterectomy (CEA).Methods Forty rabbits undergoing CEA were randomly divided into four groups (each group=10) and given a radiation dose of 0, 10, 20 and 40 Gy 32 P respectively. Rabbits were killed on the 3rd, 7th, 14th, 28th and 56th day after operation. The specimens were collected and histopathologic examinations were done.Results Proliferation apparently occurred in the intima and media of carotid the lumen became narrow in the control group on the 14 th, 28 th and 56 th day after operation. While in the radiation groups, proliferation was apparently suppressed and the lumen was much less narrowed ( P <0.05). The apoptosis rate of SMCs and PCNA positive cells increased on the 3rd day after operation and reached the peak on the 7th day. There was statistical difference between the ER groups and control group ( P <0.01). The effects were much more evident in 20 Gy and 40 Gy groups compared with 10 Gy group ( P <0.01).Conclusion ER may prevent RS by suppressing SMC proliferation and migration as well as inducing SMC apoptosis. The effects are positively correlated with radiation doses. SMC proliferation and apoptosis occur in the early period after balloon injury, while hyperplasia of intima and medial happens later.