^(192)Ir高线量率血管腔内照射对抑制兔血管平滑肌细胞增殖及新生内膜过度增生的研究

Prevention of smooth muscle cell proliferation and neointimal hyperplasia by ^(192)Ir-HDR intra-arterial irradiation in rabbit

目的 研究192 Ir高线量率血管腔内照射对用切割球囊导管行经皮血管腔内成形术(PTA)后的日本白兔髂动脉平滑肌细胞增殖抑制的经时反应和效果。方法 2 0只日本白兔经左侧颈总动脉放置切割球囊导管行髂动脉PTA术 ,随机于一侧髂动脉施行 12Gy剂量的血管腔内照射 ,非照射侧作为对照侧。实验动物于术后 1、2、3、4、8及 12周处死。根据新生内膜的形成情况 ,血管成形术后接受血管腔内照射的血管段按时间分为 3组 :即 1周组 5只、2～ 4周组 9只、8～ 12周组 6只。随后对标本进行了组织病理、形态学测量和免疫组织化学分析。结果 1周时 ,与照射侧比较 ,对照侧血管段创口修复处可见明显的新生内膜增生 ,新生内膜中抗增殖细胞核抗原 (PCNA)阳性细胞率呈一峰值 ;2～ 4周期间 ,与对照侧比较 ,照射侧血管段新生内膜增生明显减弱 (P <0 .0 1) ,新生内膜中PCNA阳性细胞率较对照侧低 ,差异有显著性意义 (P <0 .0 1) ;8～ 12周 ,照射侧血管段增生的新生内膜较对照侧仍处较低水平 ,新生内膜中PCNA阳性细胞率约低于 1%。经抗平滑肌细胞α胶原免疫组织化学染色 ,证实新生内膜中主要为平滑肌细胞。结论 由照射所致的新生内膜增生过程的抑制作用从开始时即已启动。 12Gy的192

Objective To study the temporal responses and the efficacy of 192 Ir-HDR endovascular irradiation for preventing smooth muscle cell proliferation of rabbit iliac arteries after PTA with a cutting balloon catheter. Methods A total of 20 Japanese white rabbits were used in the study. Angioplasty was performed in bilateral iliac arterial segments with cutting balloon catheter. Endovascular irradiation with 12Gy was randomly performed in one side of iliac arterial segment and the unirradiated side was studied as a control. Animals were euthanatized at 1, 2, 3, 4, 8 and 12 weeks after angioplasty. Histopathologic, morphometric, and immuno-histochemical analyses were carried out. Results At one week, histopathology showed repair of the dissection by cellular accumulation, and the neointima area had markedly increased, and a peak of PCNA-positive ratio was in the arterial segments of control groups. At 2-4 weeks, a marked and statistically significant decrease of the neointima area and the neointimal PCNA-positive ratio was observed in the irradiated arteries compared with that of control arteries (P<0.01). After 8 weeks, a significant difference of the neointima was noted between the irradiated arterial segments and the control arterial segments, the PCNA-positive ratio was below 1% in both irradiated arterial segments and the control. Conclusion The results strongly suggest that irradiation inhibit the proliferation process from the beginning. 192 Ir-HDR afterloading irradiation with a dose of 12 Gy can be considered sufficient for inhibiting neointimal hyperplasia in angioplastied rabbit iliac arteries with cutting balloon catheter.