bFGF联合骨髓干细胞动员剂促进兔缺血后肢血管新生的研究

目的: 观察局部应用碱性成纤维细胞生长因子（bFGF）联合干细胞动员剂对促进兔缺血后肢血管新生的作用。方法: 40只大耳白兔均切断左侧股动脉及其分支，制作兔后肢缺血模型。成模后随机分4组(每组10只):(1)bFGF组,在缺血后肢肌内多次注射重组人bFGF蛋白;(2)G-CSF组,皮下注射重组人粒细胞集落刺激因子（rhG-CSF）;(3) bFGF+G-CSF组，按bFGF组和G-CSF组的方法给予bFGF和G-CSF;（4）对照组，给予等量生理盐水。术后4周，各组兔行腹主动脉造影，观察侧支血管形成情况。取内收肌和腓肠肌肌组织行病理切片检查;用图像分析系统统计血管密度;用免疫组化检测内收肌和腓肠肌中VEGF阳性表达的血管数。结果: 兔侧支循环血管条数、血管密度及VEGF阳性表达的血管数均依次为：bFGF+G-CSF组 > bFGF组 > G-CSF组 > 对照组 (均P<0.05)。结论: 在缺血下肢肌内注射bFGF蛋白和皮下注射骨髓干细胞动员剂均可促进血管新生，改善肢体缺血状态;但在骨髓干细胞动员的同时，联合应用bFGF蛋白效果更好，缺血肢体改善更明显。

Co-application of basic fibroblast growth factor (bFGF) and mobilization of bone marrow stem cells to improve the angiogenesis of ischemic limbs

Objective To evaluate the effect of local co-application of basic fibroblast growth factor (bFGF) and mobilized bone marrow stem cells on angiogenesis in ischemic limbs of rabbits. Method After ischemia models were induced by surgical section and ligation of left femoral artery and its branches in 40 rabbits, they were randomized to receive intramuscular injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (n=10) in ischemic zone, hypodermic injection of recombinant human G-CSF (n=10) , co-application of bFGF and G-CSF (n=10), or normal saline (n=10). Four weeks later, angiogenesis of ischemia models was observed and evaluated by abdominal aortography, histopathologic analysis and immunohistochemical studies with the antibodies of VEGF. Results The member of capillaries, the compensatory circulation blood vessel and the vascular endothelial cells that expressed VEGF protein in bFGF G-CSF group was the most(P<0.05), that of bFGF group was more than that of G-CSF group(P<0.05), and that of saline group was the least (P<0.05). Conclusion Both intramuscular injection of recombinant human bFGF and hypodermic injection of recombinant human G-CSF (mobilization of bone marrow stem cells) can stimulate angiogenesis of the ischemic limbs. But the effect will be better if co-application of them is used.