首页> 中文期刊> 《中国介入心脏病学杂志》 >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

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

             

摘要

Objective To evaluate the efficacy and safety of endovascular brachytherapy using a simple system of a 32 P or 90 Y liquid-filled balloon catheter on the prevention of restenosis after interventional therapy. To observe the dose-effectiveness relation and to investigate its possible mechanisms. Methods In the balloon-injuried rabbit model, Eighteen balloon-injuried rabbits were used in the study, 32 P or 90 Y 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 liquid 32 P or 90 Y-filled balloon catheter system could prevent restenosis, the mechanism may be due to inhibit the proliferation of neointima and the vascular negative remodeling.%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);8 Gy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、16 Gy及24 Gy血管段PCNA阳性细胞百分率分别为(84±5)%、(77±3)%、(44±5)%和(21±6)%,除对照血管段和8 Gy血管段之间差异无显著性(P>0.05)外,其余各组间差异均有非常显著性(P<0.01),且存在剂量效应关系。未发现与放射治疗相关的不良病理改变。结论 放射性液体球囊在一定的吸收剂量范围内确可安全有效地防治血管成形术后再狭窄的形成,表现为抑制新生内膜形成和管腔面积丢失,且存在一定的剂量效应关系;其作用机制可能是通过抑制血管壁过度扩张后细胞的增殖,分泌功能和改善血管重塑形成。

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