骨髓单个核细胞对脑梗死小鼠神经元变性死亡的影响  

The effects of bone marrow mononuclear cells on neurodegeneration after ischemia in mice

作　　者：王建平[1] 欧春影[1] 蒋超[1] 余列[1] 王梦涵[1] 李魁[1] 韩伟[1] 付晓杰[1] 王新新[1] 左方芳 

机构地区：[1]郑州大学第五附属医院神经内科,郑州大学脑血管病研究所 ,郑州450052

出　　处：《中华行为医学与脑科学杂志》2013年第11期961-964,共4页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：基金项目：国家自然科学基金项目（81271284）

摘　　要：目的研究骨髓单个核细胞（BMMNCs）对脑梗死小鼠神经元变性死亡的影响。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IL-10、VEGF和IGF-1的能力。脑梗死后6h经尾静脉注射BMMNCs或PBS，脑梗后1，4，7d采用神经功能损害评分表（mNSS）、免疫荧光法、Fluoro—JadeB（FJB）染色进行神经功能、小胶质细胞活性及神经元变性死亡数目的评估。脑梗死后7d，TTC染色评价脑梗死体积。结果（1）BMMNCs在常氧或低氧条件下培养24h后，低氧环境下BMMNCs分泌细胞因子（IL-10、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治疗组相比，BMMNCs治疗组小鼠在脑梗死后第4，7天的mNSS评分、小胶质细胞的活性、神经元变性死亡数量均显著降低，差异有统计学意义（P〈0．05）；（3）BMMNCs治疗组小鼠脑梗死体积[（27．8±7．5）％]明显小于PBS治疗组[（37．1±6．9）％]，差异有统计学意义0P〈0．05）。结论骨髓单个核细胞可通过分泌细胞因子IL-10、VEGF和IGF-1抑制小胶质细胞的活性，明显抑制脑梗死后神经元的变性死亡，减少脑梗死体积，促进神经功能恢复。Objective To investigate the effects of bone marrow mononuclear cells （BMMNCs） on neuro- degeneration after cerebral 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 BMMNCs including interleukin-10 （ IL-10）, vascular endothelial growth factor （VEGF） and insuliulike growth factor-I （ IGF-1 ） were tested by en- zyme-linked immunosorbent assay （ELISA） under normoxic or hypoxic conditions.Mice were injected with PBS or BMMNCs via tail vein 6 h after ischemia reperfusion.Neurological functional deficits, the activity of microglial cell and neurodegenration were assessed on day 1,4,7 after MCAO,and infarct volume was assessed on day 7.Results （ 1 ） Compared with BMMNCs under normoxic conditions, BMMNCs under hypoxic conditions secreted more IL-10, VEGF, IGF-1 after 24h of cuhivation（P〈0.05）. （2） BMMNCs transplantation significantly reduced neurologic func- tional deficits and the number of activated microglia and degenerated neurons on days 4,7 compared with PBS trea- ted groups （P〈0.05）. （ 3 ） Compared with PBS treated group （ （ 37.1 ± 6.9 ） % ）, BMMNCs transplantation signifi- cantly reduced infarct volume（（27.8±7.5）%） （P〈0.05）.Conclusion Bone marrow mononuclear cells can signifi- cantly inhibit neurodegeneration, promote neurological recover and reduce infarct volume through inhibition of mi- croglial cell activation by secretion of cytokines including IL-10,VEGF and IGF-1.

关 键 词：脑梗死 骨髓单个核细胞 细胞移植 细胞因子 小胶质细胞 神经元变性死亡 

分 类 号：R743.3[医药卫生—神经病学与精神病学]