VEGF和反义c-myc对移植血管狭窄的影响

The effect of vascular endothelial growth factor and c-myc antisense oligodeoxynueleotides on vein graft stenosis

目的:探讨联合应用血管内皮生长因子(Vascular endothelial growth factor,VEGF)基因和c-myc反义寡核苷酸(Anti-sense oligodeoxynucleotides,AODN)对移植血管狭窄的影响。方法:选40只新西兰雄性白兔随机分为对照组(A组)、VEGF组(B组)、反义c-myc组(C组)、VEGF加反义c-myc组(D组),每组10只;将同一只兔的左、右髂外动脉各1 cm对换移植,移植血管用VEGF和(或)c-myc-AODN液浸泡转染;术后4周显微镜下测量移植血管的内膜厚度、内膜面积和移植血管狭窄率,并用免疫组化法染色计数VEGF和c-myc阳性细胞数。结果:D组移植血管的内膜厚度、内膜面积、管腔狭窄程度和c-myc阳性细胞数均明显低于A、B、C组,同时D组移植血管的VEGF阳性细胞数明显高于其它组。结论:联合应用VEGF和c-myc-AODN基因治疗能有效抑制移植血管平滑肌细胞(Vacular smooth muscle cells,VSMC)增殖,阻止内膜增生,防止移植血管狭窄。

Objective： To investigate the effect of vascular endothelial growth factor （ VEGF ） and c-myc antisense oligodeoxynucleotides （ AODN ） on vein graft stenosis.Methods ： Forty male Zelanian rabbits were randomly divided into 4 groups （ n=10 in each group ） ： control group （ group A ）, VEGF group （ group B ）, c-myc-AODN group （ group C ）, VEGF adding c-myc-AODN group （ group D ） .The left and right external iliac arteries of rabbits were transplanted reciprocally, and each transplanted vessel was 1 cm long.Then the transplanted vessels were respectively soaked in Lipofectamine, VEGF, c-myc-AODN and VEGF adding c-myc-hODN solution.Four weeks later,the intimal thickness and area, stenosis ratio of transplanted vascular were calculated and analyzed statistically among groups by computer system. The number of positive cells of VEGF and c-myc was counted by immunohistochemistry method.Results：The intimal thickness and area, stenosis ratio of the transplanted vessels, the number of c-myc positive cells in group D were significandy decreased as compared with other groups, while the number of VEGF positive cells in group D was markedly increased than other groups. Conclusion： Combination application of VEGF and c-myc-AODN could significantly inhibit the proliferation of vascular smooth muscle cells （ VSMC ） and stenosis of transplanted vessles.