骨髓动员在糖尿病小鼠缺血肢体新生血管形成中的作用  

Role of bone marrow mobilization in the angiogenesis in ischemic hindlimbs of diabetic mice

作　　者：张楠[1] 张鸿坤[2] 

机构地区：[1]浙江大学医学院附属邵逸夫医院内分泌科,杭州310016 [2]浙江大学医学院附属第一医院血管外科

出　　处：《中华内分泌代谢杂志》2006年第6期578-581,共4页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金资助(30300335);浙江省卫生厅青年人才专项基金资助(2004QN008)

摘　　要：目的探讨骨髓动员在糖尿病小鼠缺血肢体新生血管形成中的作用。方法采用链脲佐菌素建立糖尿病鼠模型,切除一侧肢体股动脉,注射粒细胞集落刺激因子(G-CSF)进行骨髓动员,以观察缺血肢体新生血管的形成。结果糖尿病小鼠模型建立8周后,血浆一氧化氮(NO)水平开始下降,骨髓动员后8 d,外周血CD^+_(34)细胞明显增加[从(0．15±0．05)%到(2．30±0．41)%],半定量RT-PCR检测缺血肢体肌肉组织的血管内皮细胞生长因子mRNA表达与正常对照组比较明显增强；动员后2周,激光多普勒血流检测骨髓动员组的缺血肢体血流明显高于未动员组[(76．37±6．10)%vs(18．07±3．40)%,P＜0．05],vWF免疫组化微血管密度检测动员组也明显高于未动员组[(26．6±4．8)个/每视野vs(11．5±2．6)个/每视野,P＜0．05]。结论糖尿病能降低小鼠血管内皮细胞的功能,但骨髓动员能促进糖尿病小鼠缺血肢体的新生血管形成。Objective To investigate the angiogenesis effect induced by bone marrow mobilization on the ischemic hindlimbs of diabetic mice. Methods Diabetes mellitus was induced in mice by injection of streptozotocin. To observe the anglogenesis effect in ischemic limbs, unilateral femoral artery and all the side branches were excised and then was given granulocyte-colony stimulating factor （G-CSF） for bone marrow mobilization. Results The level of nitric oxide （NO） in plasma was significantly lowered 8 weeks after establishment of diabetes mellitus. After mobilization for 8 days, CD34^＋ cells in peripheral blood of mice were increased significantly [ from （ 0. 15 ± 0.05 ） % to （2.30 ± 0.41 ） % ], the vascular endothelial growth factor （VEGF） mRNA level of ischemic limb, which was examined with semi-quantitative RT-PCR, became higher in diabetic mice than that in non-diabetic mice. Two weeks following mobilization, the blood perfusion detected by LASER Doppler perfnsion scan in the ischemic hindlimbs was significantly higher in the diabetic mice than in that the nondiabetic mice [ （ 76.37 ± 6.10） % vs （ 18.07 ± 3.40 ） %, P 〈 0.05 ], vWF immunohistochemical staining showed that the density of capillaries was significantly greater in the mobilization group than that in the non- mobilization group E （26.6 ± 4.8 vs 11.5 ± 2.6 ）/per field, P 〈 0.05 3. Conclusion Diabetes mellitus reduced the modulatory role of the endothelium in mice, but therapeutic angiogenesis induced by bone marrow mobilization could be an effective treatment for ischemic limb disease in diabetic mice.

关 键 词：骨髓动员 肢体缺血 糖尿病 实验性 新生血管形成 

分 类 号：R587.1[医药卫生—内分泌]