32P液体球囊血管内照射对血管损伤后管壁基质金属蛋白酶9表达的影响

目的观察血管内液体球囊放射治疗对血管成形术后再狭窄的影响,同时通过观察放射治疗效应探讨放射治疗防止再狭窄发生的可能机制.方法雄性Wistar大鼠72只,体重300～350 g,随机分为两组,胸主动脉经球囊损伤(损伤组),球囊损伤加32P液体球囊血管内照射(照射组,按照射剂量分为20 Gy亚组和28Gy亚组).使用原位杂交方法测定管壁基质金属蛋白酶9(MMP-9)mRNA表达;采用免疫组化的方法测定增殖细胞核抗原(PCNA)表达阳性细胞;用计算机图像分析方法观察血管组织形态学的变化,并对原位杂交和免疫组化的结果进行定量分析.结果照射组与损伤组相比第14天外弹力板围绕面积、管腔面积明显增大,且随照射剂量的增加而增大;第1,3,7天管壁MMP-9 mRNA表达率明显降低,降低程度随照射剂量增加而增大.结论32P液体球囊可防止再狭窄的形成,其机制之一可能是通过抑制管壁MMP-9 mRNA表达,从而抑制血管重塑.

Experimental study of endovascular irradiation using liquid 32P-filled balloon catheter

Objective:To evaluate the effects of endovascular irradiation on restenosis after interventional therapy and investigate the possible mechanism of restenosis prevention of endovascular irradiation. Method: Balloon injury was performed on rat thoracic aorta. The rats were divided into irradiated group, followed immediately by ionizing radiation using liquid 32P-filled balloon catheter, and injured group, not followed by ionizing radiation. In situ hybridization method was used to detect the mRNA expression of matrix metalloproteinase-9(MMP-9) in the vessel. The proliferation of vascular cells was evaluated by means of immunohistochemistry of the proliferation of cellular nuclear antigen(PCNA). Pathological sections of thoracic aorta were observed to estimate the changes of vascular histomorphology by computer analysis of photomicrogram. The expression of MMP-9mRNA and PCNA was analyzed by image analysis. Result:Founteen days after injury, morphometric analysis indicated that the lumen area and external elastic lamina (EEL) area of the irradiated vessels were significantly larger than that of non irradiated vessels, and these changes appear dose-dependent increase. 1, 3, 7days after injury, there were fewer mRNA expression of MMP-9 in the irradiated vessels, with dose-dependent decrease, than in nonirradiated ones. Conclusion: Endovascular irradiation using liquid 32P-filled balloon catheter system could prevent restenosis. One of its mechanism might be improvement on vascular remodeling, through inhibiting the expression of MMP-9 mRNA.