目的 探讨粒细胞集落刺激因子(G-CSF)联合神经干细胞(NSCs)移植治疗新生大鼠缺氧缺血性脑病(HIE)的疗效,为临床更有效的治疗HIE提供理论基础.方法 新生7d的SD大鼠建立重度HIE模型后,分为对照组、G-CSF组、NSCs组和G-CSF+NSCs组.G-CSF组在建模后1h皮下注射G-CSF 50 μg/(kg·d),共5 d；NSCs组在建模后第2天经脑室移植NSCs; G-CSF+NSCs组则在每天注射G-CSF的基础上进行NSCs移植；对照组注射等量生理盐水.在建模1、2和4周后通过脑重和mNSS评分分析治疗效果,并在建模4周后对大鼠脑组织行冰冻切片进行病理学分析.结果 建模l、2和4周后,对照组大鼠的脑重明显低于其他三组,且4周后NSCs组、G-CSF+NSCs组大鼠脑重高于G-CSF组,差异均有统计学意义(P＜0.01).建模1、2和4周后,对照组大鼠mNSS评分显著高于其他三组；建模2、4周后,G-CSF+NSCs组大鼠mNSS评分低于G-CSF组,差异均有统计学意义(P＜0.05).病理检查显示,G-CSF+NSCs组神经细胞排列最整齐,未见变性坏死的神经细胞.结论 单独G-CSF或NSCs移植均可减轻HIE的神经损伤症状,联合治疗可取得最佳疗效.%Objectives To explore the efficacy of granulocyte colony stimulating factor (G-CSF) combined with neural stem cells (NSCs) transplantation for severe hypoxic ischemic encephalopathy (HIE) in neonatal rats, so as to provide the theoretical basis for HIE treatment. Methods After the establishment of severe HIE model, the 7-day-old SD rats were randomly divided into four groups, the control group, G-CSF group, NSCs group and G-CSF+NSCs group. The rats in G-CSF group were injected subcutane-ously with 50 μg/kg G-CSF once a day for 5 days, starting 1 hour after the establishment of HIE model The rats in NSCs group and G-CSF+NSCs group were given NSCs transplantation 1 day after the establishment of model and the rats in G-CSF+NSCs group were also given injection of G-CSF once a day. The rats in the control group received injection of equivalent volumes of normal saline once a day. Therapeutic effect was analyzed using brain weight and mNSS score. 1,2 and 4 weeks after the establishment of model. Pathological changes in frozen sections of the rat brains were analyzed 4 weeks after the challenge. Results The brain weights of rats in other three groups were significantly higher than those in control group 1,2 and 4 weeks after the establishment of model (P<0.0l), and furthermore the brain weights of rats in NSCs group and G-CSF+NSCs group were significantly higher than those in G-CSF group 4 weeks after the establishment of model (P<0.01). The mNSS scores of rats in control group were significantly higher than those in other three groups 1, 2 and 4 weeks after the establishment of model (P＜0.0l). The mNSS scores of rats in G-CSF+NSCs group were significantly lower than those in G-CSF group 2 and 4 weeks after the establishment of model (P<0.05). The most orderly arrangement of nerve cells was seen and no cellular degeneration and necrosis were found in rats of G-CSF+NSCs group by pathological examination. Conclusions Either G-CSF or NSCs transplantation can reduce the nerve injury of HIE. However, the combined treatment of G-CSF and NSCs may have the best efficacy.
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