Mechanism of inhibiting neointimal proliferation with intra-arterial irradiation using rabbit iliac arteries

为评价192 Ir-HDR动脉内照射对切割球囊导管经皮腔内血管成形术（PTA）后内膜增生的影响，采用兔髂动脉进行了实验研究。在家兔双侧髂动脉段进行PTA。对一侧髂动脉段进行6 Gy或12 Gy的动脉内照射，并以未照射侧作为对照。6 Gy组存活至1、2、4周处死。12 Gy组分别于术后1、2、4、8、12周处死。进行组织病理学、形态计量学和免疫组织化学分析。组织学显示，与对照动脉相比，受照动脉的细胞积聚修复了夹层，新生内膜增殖量显著减少。在一周时，对照动脉的新生内膜面积显著增加。在辐照动脉段中没有新生内膜增殖的证据。在2-4周时，与对照动脉相比，在照射组中观察到新生血管瘤面积的显著和统计学上显著的减少（p<0.001）。12 Gy组8-12周时与对照组比较有显著性差异。12 Gy组对照动脉段新生内膜PCNA阳性率于1周达高峰。在2-4周时，与照射动脉相比，对照动脉段的新生内膜PCNA阳性率仍然显著增加。8周后，照射和对照动脉中PCNA阳性率均低于1%。结果表明，6- 12 Gy的192 Ir-HDR后装照射可有效抑制血管成形术后兔髂动脉内膜增生。

To evaluate effect of 192Ir-HDR intra-arterial irradiation for preventing neointimal proliferation percutaneous transluminal angioplasty (PTA) with cutting balloon catheter, experimental study was performed using rabbit iliac arteries. PTA was underwent in the both iliac arterial segments of rabbits. Intra-arterial irradiation with 6Gy or 12Gy was performed on one side of iliac artery segment and unirradiated side was studied as a control. Rabbits of 6Gy group survived until sacrifice at 1, 2, and 4 weeks. Rabbits of 12Gy group were euthanatized at 1, 2, 4, 8 and 12 weeks after PTA. Histopahologic, morphometric and immunohistochemical analyses were carried out. Histopathlogy showed repair of dissection by cellular accumulationand and a striking reduction in the amount of neointimal proliferation in irradiated arteries compared with control arteries. At one week, neointima area had markedly increased in control arteries. There was no evidence of neointimal proliferation in irradiated arterial segments. At 2-4 weeks, a marked and statistically significant decrease in neoientima area was observed in irradiated groups compared with control arteries(p<0.001). A significant difference was noted between irradiated arterial segments and control arteries at 8-12 weeks in 12Gy group. In 12Gy group, threre was a peak of PCNA-positive ratio in neointima of control arterial segments at one week. At 2-4 weeks, neointimal PCNA-positive ratio was still significantly increased in control arterial segments compared with irradiated arteries. After 8 weeks, PCNA-positive raio was below 1% in both irradiated and control arteries. From these results, 192Ir-HDR afterloading irradiation with a dose of 6-12Gy can be considered sufficient for inhibiting neointimal proliferation in angioplastic rabbit iliac arteries with cutting balloon catheter.