BMSCs移植对大鼠脊髓损伤后VEGF表达及细胞凋亡的影响Effects of bone marrow stromal cells transplantation on the expression of vascular endothelial growth factor and apoptosis of cells after spinal cord injury in rats
于德水;吕刚;曹阳;王岩峰;智晓东;范仲凯;
摘要(Abstract):
[目的]研究骨髓基质细胞(BMSCs)移植对大鼠脊髓损伤(SCI)后血管内皮生长因子(VEGF)蛋白表达及神经细胞凋亡的影响,探讨骨髓基质细胞移植治疗脊髓损伤的机制。[方法]取大鼠股骨和胫骨骨髓培养BM-SCs并传代。参照Taoka′s方法制作大鼠脊髓压迫损伤模型。脊髓损伤后30 min,进行BMSCs或DMEM培养液损伤周围注射。术后3、7和14 d,应用Western Blot法检测损伤脊髓组织内VEGF蛋白的表达,应用TUNEL方法检测脊髓损伤周围神经细胞凋亡情况。[结果]移植术后3、7、14 d,BMSCs组VEGF蛋白的表达水平呈时间依赖性增加,与DMEM组相比,术后3 d两组VEGF蛋白表达水平没有显著性差异(P>0.05),而术后7和14 d,BMSCs组VEGF蛋白表达水平显著高于DMEM组(P<0.01)。此外,与DMEM组大鼠相比,移植术后3、7和14 d,BMSCs移植显著减少脊髓损伤周围区凋亡的神经细胞数目(P<0.05)。[结论]脊髓损伤后,BMSCs移植能够增加VEGF蛋白的表达并且抑制神经细胞凋亡。
关键词(KeyWords): 脊髓损伤;骨髓基质细胞;细胞移植;血管内皮生长因子;凋亡
基金项目(Foundation): 教育部高校博士学科点专项科研基金项目(编号:20060159019);; 辽宁医学院第一临床学院青年科技启动基金(2010)
作者(Author): 于德水;吕刚;曹阳;王岩峰;智晓东;范仲凯;
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参考文献(References):
- [1]Zacharek A,Chen J,Cui X,et al.Angiopoietin1/Tie2 and VEGF/Flk1induced by MSC treatment amplifies angiogenesis and vascular stabili-zation after stroke[J].J Cereb Blood Flow Metab,2007,10:1684-1691.
- [2]Liu Y,Dulchavsky DS,Gao X,et al.Wound repair by bone marrowstromal cells through growth factor production[J].J Surg Res,2006,2:336-341.
- [3]李国良,陈俊,杨松巍.静脉移植骨髓间充质干细胞促进脊髓损伤后GDNF基因的表达[J].中国矫形外科杂志,2007,4:1871-1873.
- [4]Zachary I.Neuroprotective role of vascular endothelial growth factorsignalling mechanisms biological function and therapeutic potential[J].Neurosignals,2005,14:207-221.
- [5]Ding XM,Mao BY,Jiang S,et al.Neuroprotective effect of exogenousvascular endothelial growth factor on rat spinal cord neurons on vitrohypoxia[J].Chin Med J,2005,19:1644-1650.
- [6]Jin K,Mao XO,Greenberg DA.Vascular endothelial growth factorstimulates neurte outgrowth from cerebral cortical neurons via Rho ki-nase signaling[J].J Neurobiol,2006,66,236-242.
- [7]Widenfalk J,Lipson A,Jubran M,et al.Vascular endothelial growthfactor improves functional outcome and decreases secondary degenera-tion in experimental spinal cord contusion injury[J].Neuroscience,2003,120:951-960.
- [8]Liu Y,Figley S,Spratt SK,et al.An engineered transcription factorwhich activates VEGF-A enhances recovery after spinal cord injury[J].Neurobiol Dis,2010,2:384-393.
- [9]Park HW,Lim MJ,Jung H,et al.Human mesenchymal stem cell-de-rived Schwann cell-like cells exhibit neurotrophic effects,via distinctgrowth factor production,in a model of spinal cord injury[J].Glia,2010,9:1118-1132.
- [10]Dasari VR,Spomar DG,Cady C,et al.Mesenchymal stem cells fromrat bone marrow downregulate caspase-3-mediated apoptotic pathwayafter spinal cord injury in rats[J].Neurochem Res,2007,12:2080-2093.