MMP-2、TIMP-2与^(32)P液体球囊照射预防血管成形术后再狭窄的关系研究

The study on relation of MMP-2, TIMP-2 and brachytherapy with ^(32)P liquid filled balloon preventing restenosis after angioplasty

目的探讨放射治疗——32P液体球囊血管内近距离照射预防血管成形术后再狭窄,以及在此过程中基质金属蛋白酶(MMP-2)及其抑制因子(TIMP-2)的变化与作用。方法建立兔双侧髂动脉动脉粥样硬化狭窄模型,大耳白兔24只,分为3组:9.1Gy组、21.8Gy组、33.4Gy组。随机选择一侧髂动脉行球囊扩张血管成形术,行血管内近距离照射治疗,另一侧髂动脉球囊扩张血管成形后作为自身对照。行血管造影术观察双侧髂动脉血管再狭窄的程度,对MMP-2 mR-NA和TIMP-2 mRNA进行半定量分析。结果①血管造影显示照射剂量21.8Gy组血管再狭窄程度最轻,与对照组血管差异有显著性(P<0.01)。②用原位杂交法对MMP-2mRNA、TIMP-2mRNA进行半定量分析,在照射剂量21.8Gy组MMP-2mRNA染色阳性面积最小,TIMP-2mRNA染色面积最大,均与对照亚组差异有显著性(P<0.01)。结论应用32P放射性液体球囊行血管内近距离照射在一定剂量范围内可以有效地抑制血管成形术后再狭窄。

Objective To study the relation between endovascular brachythrapy with 32P liquid filled balloon and restenosis, at the same time investigate the changes and the effection of matrix metalloproteinases and it’s tissue inhibitors during this course. Methods A total of 24 rabbits injured of double iliac arteries with balloon, were fed with cholesterol food for six weeks. They were divided into three groups： 9.1 Gy, 21.8 Gy, 33.4 Gy. Angioplasty and 32P brachytherapy were procedured at one side randomly, the other side non-radioactive therapy was served as self-controlled. The iliac artery angiography was performed to observe the target vessel restenosis degree. The matrix metalloproteinase-2 and its inhibitor level were tested with in situ hybridization. Results After five weeks of brachytherapy, the results were： ①Angiography： comparatively, the average luminal diameter stenosis in 21.8 Gy group was the slightest （P〈0.01）. ②In situ hybridization results： in 21.8 Gy group, the percentage of MMP-2 mRNA positive areas by staining was the smallest and that of the inhibitor was the largest （P〈0.01）. Conclusion Endovascular brachytherapy at proper dose with filled balloon catheter system could prevent restenosis significantly after angioplasty.