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

兔髂动脉动脉内照射抑制内膜增殖的机制

• 批准号: 13670971
• 负责人: OGUCHI Manabu
• 金额: $ 1.34万
• 依托单位: KANAZAWA MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670971/
• 关键词: Ir-192 high dose rate; intra-arterial irradiation; rabbit iliac artery; neointimal proliferation; 192-Ir高線量率照射; 日本白色家兎; 平滑筋細胞; 超高圧X線; 外部照射; カッティングバルーンカテ

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.

为了评价 192Ir-HDR 动脉内照射预防内膜增殖的效果，采用切割球囊导管进行经皮腔内血管成形术（PTA），以兔髂动脉为实验对象进行了实验研究。对家兔的双髂动脉段进行 PTA。对一侧髂动脉段进行6Gy或12Gy的动脉内照射，并以未照射侧作为对照。 6Gy组的兔子均存活至1、2、4周处死。 12Gy组于PTA后1、2、4、8、12周处死。进行了组织病理学、形态测量和免疫组织化学分析。组织病理学显示，与对照动脉相比，受辐射动脉中的夹层通过细胞积累得到修复，并且新内膜增殖量显着减少。一周后，对照动脉的新内膜面积明显增加。在受辐射的动脉段中没有新内膜增殖的证据。 2-4 周时，与对照动脉相比，照射组的新血管面积显着且具有统计学意义的减少（p<0.001）。 8-12 周时，12Gy 组的受照射动脉段与对照动脉之间存在显着差异。 12Gy组对照动脉段新生内膜PCNA阳性率在1周时出现峰值。 2-4周时，与照射动脉相比，对照动脉段的新内膜PCNA阳性率仍然显着增加。 8 周后，受照射动脉和对照动脉中 PCNA 阳性比率均低于 1%。从这些结果来看，6-12Gy 剂量的 192Ir-HDR 后装照射足以抑制切割球囊导管血管成形兔髂动脉的新生内膜增殖。