粒细胞集落刺激因子对人神经干细胞移植后新生大鼠体内神经元分化的影响

摘要

目的 观察粒细胞集落刺激因子(G-CSF)对移植的人神经干细胞(hNSCs)新生大鼠体内神经元分化的影响.方法 出生1周的Wistar大鼠建立缺氧缺血性脑损伤(HIBD)模型,建模后分成2组:NSC移植组(N组,n=17)和NSC移植+G-CSF治疗组(NG组,n=16).NG组大鼠建模后1 h即皮下注射G-CSF,50 μg·kg-1,1次·d-1,移植前后连续5 d注射G-CSF.2组大鼠均于建模后第2天经脑室移植hNSCs.移植后1周、2周采用免疫荧光法观察2组植入细胞在皮质、海马部位神经元分化情况.结果 移植后1周,分化神经元主要分布于大鼠损伤侧海马、皮质;移植后2周,神经元分化数量增多,并发出细长分枝.NG组海马各区神经元分化存活数量较N组多,差异有统计学意义(Pa<0.01);NG组皮质神经元分化存活数量在移植后2周时较N组多,差异有统计学意义(P<0.001).结论 G-CSF有利于植入大鼠脑内的hNSCs的存活,并促进植入hNSCs向神经元分化,因此联合G-CSF可能有助于进一步提高hNSC移植的疗效.%Objective To observe the effect of granulocyte - colony stimulating factor( G - CSF) on the differentiation of implanted human neural stem cells(hNSCs) into neurons.Methods These rats which were bom within a week were used to establish hypoxic -ischemic brain damage(HIBD) models, and they were divided into 2 groups randomly:the single NSC mmsplantation group( group N, n = 17 ) and the NSC transplantation + G - CSF group( group NG, n = 16).In group NG, G - CSF(50 μg · kg - 1, 1 time per day) was administered 1 hour after performing operation subcutaneously once a day for 5 days in a row.In both groups,there rats received implantation of hNSCs into the left cerebral ventricles on the second day after the operation.The neural differentiation of the transplanted cells in the cerebral cortex and hippocampus was detected by immunofluoreseence at 1 week and 2 weeks after the transplantation.Results Differentiated neurons of implanted cells were distributed mainly in the cortex and the hippocampus of the injured side.The numbers of differentiated neurons in the hippocampus were significantly increased in group NG compared with those in group N (Pa ＜ 0.01 ).And the number in the cortex was significantly greater in group NG than that in group N at 2 weeks after operation ( P ＜ 0.001 ).Conclusions G - CSF enhances the survival and promotes the differentiation of implanted hNSCs into neurons.G - CSF treatment may play an important role in improving the effects of hNSC implantation.