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

为了评价192Ir-HDR动脉照射对切开球囊导管经皮腔内血管成形术（PTA）预防新生内膜增生的作用，采用家兔髂动脉进行了实验研究。家兔髂动脉双段行PTA。对一侧髂动脉段进行6Gy或12Gy的动脉内照射，未照射一侧作为对照。6Gy组在1、2、4周存活至牺牲。12Gy组于PTA后1、2、4、8、12周实施安乐死。进行组织病理学、形态计量学和免疫组织化学分析。组织病理学显示，与对照动脉相比，受辐射动脉的细胞积聚修复了夹层，新生内膜增生的数量显著减少。一周后，对照动脉新生内膜面积明显增加。未见辐照动脉段内膜增生的证据。在2-4周时，与对照动脉相比，照射组的新生瘤面积明显减少，具有统计学意义（p<0.001）。12Gy组照射动脉段与对照动脉在8-12周有显著差异。12Gy组对照动脉段新生内膜pcna阳性率在1周达到峰值。在2-4周时，对照动脉段的新内膜pcna阳性比率仍明显高于辐照动脉。8周后，放射动脉和对照动脉的pcna阳性比率均低于1%。由此可见，6-12Gy剂量的192Ir-HDR辐照后足以抑制切开球囊导管血管成长性家兔髂动脉内膜增生。

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.