骨髓单个核细胞分泌细胞因子对脑梗死后小鼠细胞分化的影响  

The effects of cytokines produced by bone marrow mononuclear cells on differentitation after ischemia in mice

作　　者：刘玉府[1,2] 欧春影[1,2] 韩伟[1,2] 

机构地区：[1]郑州大学第五附属医院 [2]郑州大学脑血管病研究所,河南郑州450052

出　　处：《中风与神经疾病杂志》2014年第5期392-396,共5页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学资金(81271284)

摘　　要：目的研究骨髓单个核细胞(bone marrow mononuclear cells;BMMNCs)分泌的细胞因子对脑梗死小鼠细胞分化的影响。方法将雄性昆明小鼠随机分为PBS治疗组和BMMCs治疗组。线栓法制作小鼠大脑中动脉栓塞(MCAO)模型;梯度离心法提取BMMNCs;酶联免疫吸附法(ELISA)评价常氧及低氧培养条件下BMMNCs分泌bFGF、VEGF和IGF-1的能力。脑梗死后24 h经尾静脉注射BMMNCs或PBS,脑梗死后1、4、7、14 d行神经功能损害评分(modified Neurological Severity Scores,mNSS)并评价脑组织含水量;脑梗死后7 d TTC染色评价脑梗死体积;脑梗死后14 d免疫荧光检测BMMNCs在脑内的存活、迁移、分布和分化情况。结果 (1)BMMNCs在常氧或低氧条件下培养24 h后,低氧环境下BMMNCs分泌细胞因子(bFGF、VEGF和IGF-1)的能力明显强于常氧环境,差异有统计学意义(P<0.05);(2)与PBS溶剂组相比,BMMNCs治疗组小鼠在脑梗死后4、7、14 d的mNSS评分显著降低,差异有统计学意义(P<0.05);(3)BMMNCs治疗组小鼠在4、7 d脑组织含水量明显低于PBS治疗组,差异有统计学意义(P<0.05);(4)BMMNCs能够迁移分布至小鼠脑损伤区,并分化为星形胶质细胞和小胶质细胞。结论骨髓单个核细胞可通过分泌细胞因子bFGF、VEGF和IGF-1促进细胞分化,促进神经功能恢复,减少脑梗死体积,减轻脑水肿。Objective To investigate the effects of cytokines produced by bone marrow mononuclear cells on differentitation after ischemia in mice. Methods Adult male mice were randomly divided into PBS treated group and BMMNCs treated group. The model was established with suture emboli method; BMMNCs were isolated with density gradient centrifugation method. The production of cytokines from basic fibroblast growth factor（ bFGF）,vascular endothelial growth factor（ VEGF）,insulinlike growth factor-I（ IGF-1） were tested by enzyme-linked immunosorbent assay（ ELISA） under normoxic or hypoxic conditions; Mice were injected with PBS or BMMNCs via tail vein at 24 h after ischemia reperfusion; Neurological functional deficits and brain edema were assessed on days1,4,7,14 after MCAO. Results（ 1） Compared with BMMNCs under normoxic conditions,BMMNCs under hypoxic conditions secreted more bFGF,VEGF,IGF-1 after 24h of cultivation（ P 0. 05）;（ 2） BMMNCs transplantation significantly reduced neurologic functional deficits on days 4,7,14 compared with PBS treated ischemic groups（ P 0. 05）;（ 3） BMMNCs transplantation significantly reduced brain edema on days 4,7 compared with PBS treated ischemic groups（ P 0. 05）;（ 4） BMMNCs were able to migrate into perihematoma region and differentiated into microglial cell. Conclusion Bone marrow mononuclear cells can differentiated into astrocyte and microglial cell,promote neurological recover and reduce brain edema and infract volume through the secretion of cytokines including bFGF,VEGF,IGF-1.

关 键 词：骨髓单个核细胞 脑梗死 细胞移植 细胞因子 分化 

分 类 号：R743.3[医药卫生—神经病学与精神病学]