| Objective: To assess the efficacy and safety of a novel technique for endovascular brachytherapy with 32P preventing restenosis after angioplasty and to observe the dose-effect relation , the possible mechanisms of irradiation therapy reducing restenosis. Methods:After ballon endothelial injury of double iliac arteries and six weeks cholesterol-fed in 24 rabbits.the double iliac artery atherosclerotic stenosis model was set up.We procedured angioplasty and 32P brachytherapy at one side randomly ,the absorbed doses were 9.1Gy, 21.8Gy and 33.4Gy respectively.the other side non-radiative therapy was served as self-controled.After five weeks cholesterol-fed.the iliac artery angiography was performed to observe the target vessel restenosis degreepathological sections of iliac arteries were observed with light-microscope, transmisson electron; and nuclear factor- K B(NF- K B, insulin like growth-1(IGF-1) was stained using immunohistochemical techniques.We also measured the neointima areas, lumen areas, media areas and the percentage of NF-k B, IGF-1 positive areas by computer analysis of photomicrographs. Results:After five weeks of brachytherapy, the results showed:(1) Angiography : the average luminal diameter stenosis was 55.20+ 14.47% in control vessels;57.5?13.08% in 9.1Gy vessels;25.27?.77% in 21.8Gy vessels;78.33?14.72% in 33.4Gy vessels.(2) Light-microscope: strong neointimal proliferation and strait lumen were observed in the control vessel ;there weren't obvious changes in 9.1Gy group(P>0.05);in 21.8Gy group.the proliferation and migration of smooth muscle cells was significantly suppressed ,the neointimal areas was the smallest and the lumen areas did not decrease;however the neointima thicked to make the cavity serious stenosis, and the smooth in-4-media was shrinked and thinned in 33.4Gy group.four vessels occurred arterial thrombosis.(3) Transmission electron: in control vessel the VSMC was synthetical type, the structure was similar to apoptic body in plasma, collagen fiber was hyperplastic and fused, formed disorganized, a lot of fatty vacuoles deposited in plasma; there was no difference in 9.1Gy group(P>0.05); in 21.8Gy group the VSMC was contractive type, a lot of apoptic body could be seen in plasma,the collagen fiber was ordinal and obvious decreasing in partial area, small quantity of fatty vacuoles deposited; in 33.4Gy group the cell dissolved,membrance structure was damaged,coagulation necrosis of the cells was showed,collagen fiber was metamorphic and ruptured,fatty vacuoles was filled distributing.(4) Immunohistochemical results: the percentage of NF-KB, IGF-1positive areas by staining was 33.99?.04%,32.52+6.12% in the control respectively;32.84?.21%,28.26?.18% in 9.1Gy vessel respectively; 20.91 + 6.07%,17.17 ?6.83% in 21.8Gy vessel respectively; 7.97 ?2.53%,6.84 ?3.05% in 33.4Gy vessel respectively;and except 9.1Gy vessel compared with the control(P>0.05),the other groups compared with control(P<0.01),the dose-effectiveness relation was observed. Conclusions:Endovascular brachytherapy with 32P filled ballon catheter system could prevent restenosis after angioplasty.the mechanism may be due to reduce neointima formation and increase lumen size; inhibit the activation of NF- K B and its target gene.which reduce the proliferation and migration of smooth muscle cells;increase apoptosis and improve the vascular remodeling.
|
PDF Full Text Request