摘要
目的探讨G-CSF和AMD3100对小鼠脑梗死后骨髓来源的极小胚胎样干细胞(VSEL-SCs)的动员和募集机制。方法线栓法制备大脑中动脉栓塞(MCAO)模型,腹腔内分别注射G-CSF、AMD3100及G-CSF联合AMD3100,观察术后神经功能评分,流式细胞法计数外周血中VSEL-SCs数量;ELISA检测血浆及脑组织中SDF-1水平,免疫组化检测SDF-l阳性细胞。结果 G-CSF组神经功能评分明显降低(P<0.05);各组动员到外周的VSEL-SCs含量高于对照组(0.17%±0.01%)(P<0.05);G-CSF组在72和108 h时血浆SDF-1浓度高于对照组(P<0.05),但低于AMD3100组和G-CSF+AMD3100组(P<0.05),血浆SDF-1水平与动员到外周血的VSELs数量成正相关(P<0.05);G-CSF组、G-CSF+AMD3100组脑组织的SDF-1浓度及SDF-1阳性细胞均高于对照组(P<0.01)。结论G-CSF的脑保护作用是通过CXCR4/SDF-1轴的趋化作用使募集到梗死区的CXCR4+细胞增多来实现的。
Objective To investigate the mobilization of bone marrow very small embryonic-like stem cells(VSEL-SCs) into peripheral blood(PB)and its recruitment to the infarcted brain tissues in focal cerebral ischemia mouse.Methods Mouse middle cerebral artery occlusion(MCAO) model was induced by using the filament occlusion method.G-CSF,the CXCR4 specificity antagonist AMD3100 and combilation used were seperatedly injected to MCAO model.Neurological scale was evaluated.The number of VSEL-SCs mobilized into PB was checked by fluorescence-activated cell sorting analysis.The level of SDF-1 in plasma and cerebral tissue was determined by ELISA.Positive expression of SDF-1 in ischemic regions was detected by immunohistochemistry.Results Compared with the control group,the neurological behavioral scale of G-CSF treated group was significantly lower 108 hours after operation(P0.05).All three operated groups mobilized more VSEL-SCs into PB compared with the control group(0.17%±0.01%)(P0.05).The plasma SDF-1 density significantly incresed in G-CSF group at 72 and 108 h(P0.05)while AMD300 and A+G group show stronger effect at all three time point(24,72,108 h).Positive correlation can be seen between the number of VSEL-SCs mobilized into PB and the SDF-1 plasma concentration(P0.05).The SDF-1 level of cerebral tissue was significantly incresed in G-CSF group and the expression of SDF-1 in ischemia region was much stronger in G-CSF group and A+G group.Conclusion The mechanism of beneficial effects of G-CSF possibly related to the increasement of SDF-1 expression in the infarcted tissues and recruitment of more VSEL-SCs through CXCR4/SDF-1 axis.
出处
《基础医学与临床》
CSCD
北大核心
2011年第11期1194-1199,共6页
Basic and Clinical Medicine
基金
国家自然科学基金(31100985)
重庆市自然科学基金(2010BB5096)
重庆市卫生局科研课题(2009-2-207)
关键词
极小胚胎样干细胞
骨髓干细胞
动员
脑梗死
very small embryonic-like stem cells
bone marrow stem cells
mobilization
ischemic stroke