放射性液体球囊血管内照射防治血管成形术后再狭窄的实验研究

Experimental study of endovascular brachytherapy using irradiation liquid filled balloon catheter

目的评定放射性液体球囊防治血管成形术后再狭窄的有效性、安全性和可行性，并观察其剂量效应关系，初步探讨其作用机制。方法１８只日本大耳白兔髂动脉经球囊过度扩张损伤后，一侧行３２Ｐ或９０Ｙ放射性液体球囊血管内照射作治疗，另一侧以假源（充盈造影剂的液体球囊）未经治疗作对照。５周后重复血管造影观察血管影像学改变；原位固定取材后，分析血管断面组织形态学的变化；免疫组化方法观察增殖细胞核抗原（ＰＣＮＡ）阳性细胞以了解血管壁细胞的增殖情况；行胶原染色显示细胞外基质的合成情况。结果造影可见兔髂动脉经球囊过度扩张损伤后未经治疗的靶血管段明显狭窄，平均狭窄程度达７７％；血管壁吸收剂量为２４ Ｇｙ的靶血管段无明显狭窄或仅轻度狭窄（平均狭窄程度为 １２％），１６ Ｇｙ者为 ３０％，８ Ｇｙ者为７６％。兔髂动脉病理切片行 ＨＥ染色和弹力纤维染色，经计算机图像分析可见：血管壁吸收剂量为 ２４ Ｇｙ和 １６ Ｇｙ的靶血管段外弹力板围绕面积，内弹力板围绕面积，新生内膜面积，管腔面积分别与其自身对照相比具有统计学意义（Ｐ＜０．０１）；８Ｇｙ者与其自身对照血管段相比无统计学意义（Ｐ＞０．０５）。行ＰＣＮＡ染色可见：对照血管段，血管壁吸收剂量为 ８ Ｇｙ、１?

Objective To evaluate the efficacy and safety of endovascular brachytherapy using a simple system of a32 P or 90 Y liquid-filled balloon catheter on the prevention of restenosis after interventional therapy. To observe the dose-effectiveness and to investigate its possible mechanisms. Methods In the balloon- injuried rabbit model, Eighteen balloon-injuried rabbits were used in the study, 32P or90Y Liquid was filled into the balloon catheter system and radiative balloon was positioned on the one side of rabbit iliac artery after balloon over-stretching, on the other side non-radiative balloon inflation was served as the placebo. After five weeks, the iliac artery angiography was performed, pathological sections of iliac arteries were observed and the changes of vascular histomorphology were estimated by computer analysis of photomicrograms. Using immunohistochemical techniques, proliferating cell nuclear antigen (PCNA) was quantified to assess the proliferation of vascular smooth muscle cells, and matrix synthesis estimated by collagen staining.Results After five weeks, the target vessel of placebo stenosis 77% in average; the 24 Gy vessel 13% in average;the 16 Gy vessel 30% in average;the 8 Gy vessel 76% in average. HE-stained sections were morphometrically analyzed, the external elastic lamina (EEL) area, intimal elastic lamina (IEL) area, neointimal area, luminal area in 24 Gy and 16 Gy vessel compared with self-controlced respectively P < 0.01; in 8 Gy vessel compared with self-controlled respectively P > 0.05; except 8 Gy vessel compared with the placebo (P > 0.05), neointimal area in the other groups compared with placebo remarkably inhibited (P< 0.01), the dose-effectiveness relation was observed. The percentage of PCNA positive cells by staining was(84 ± 5 ) % in the control and(77 ± 3 ) %, (44 ± 5 ) %, (21 ± 6) % in the therapy vessel of 8 Gy, 16 Gy, 24 Gy respectively and except 8 Gy vessel compared with the placebo (P>0.05), the other groups compared with placebo (P < 0.01),the dose-effectiveness relation was observed. Conclusion A significant effect of high-energy β-radiation to reduce neointima formation and increase lumen size was observed in enough dose groups. Endovascular brachtherapy using liquid32P or 90 Y-filled balloon catheter system could prevent restenosis, the mechanism may be due to inhibit the proliferation of neointime and the vascular negative remodeling.