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粒细胞集落刺激因子可改善脊髓损伤微环境下小胶质细胞的替代激活。

Granulocyte colony-stimulating factor improves alternative activation of microglia under microenvironment of spinal cord injury.

机构信息

Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan, Shandong 250012, PR China.

出版信息

Neuroscience. 2013 May 15;238:1-10. doi: 10.1016/j.neuroscience.2013.01.047. Epub 2013 Feb 16.

Abstract

Granulocyte colony-stimulating factor (G-CSF) was investigated in the present study to examine whether it could affect the activation status of microglia under microenvironment of spinal cord injury and provide a potential therapeutic treatment for spinal cord injury. We established mouse spinal cord hemisection model and injected recombinant human G-CSF (rhG-CSF) subcutaneously. The results demonstrated that G-CSF could recruit microglia to the injury site in the first 72h after spinal cord injury. Moreover, G-CSF inhibits the expression of pro-inflammatory factors and promotes the expression of neurotrophic factors. Additionally, G-CSF also increases the expression of markers of M2 macrophage and inhibits the expression of markers of M1 macrophage in BV2 microglia in vitro model, favoring the M2 polarization of microglia under the microenvironment of spinal cord hemisection. NFκB signal pathway was involved in G-CSF-induced polarization of BV2 microglia. As a conclusion, we suggested that administration of G-CSF within the first 72h after spinal cord injury might reduce early inflammation-induced detrimental effect and promote an anti-inflammatory response that favors repair via improving alternative activation of microglia. Administration of G-CSF in the acute phase of spinal cord injury may be a promising strategy in restorative therapy after spinal cord injury.

摘要

本研究旨在探讨粒细胞集落刺激因子(G-CSF)是否能影响脊髓损伤微环境下小胶质细胞的激活状态,并为脊髓损伤提供一种潜在的治疗方法。我们建立了小鼠脊髓半切模型,并皮下注射重组人 G-CSF(rhG-CSF)。结果表明,G-CSF 可在脊髓损伤后 72 小时内招募小胶质细胞到损伤部位。此外,G-CSF 可抑制促炎因子的表达,促进神经营养因子的表达。此外,G-CSF 还可增加体外 BV2 小胶质细胞模型中 M2 巨噬细胞标志物的表达,抑制 M1 巨噬细胞标志物的表达,有利于脊髓半切微环境中小胶质细胞的 M2 极化。NFκB 信号通路参与了 G-CSF 诱导的 BV2 小胶质细胞极化。综上所述,我们认为在脊髓损伤后 72 小时内给予 G-CSF 可能通过改善小胶质细胞的替代激活来减轻早期炎症诱导的有害作用,并促进有利于修复的抗炎反应。在脊髓损伤的急性期给予 G-CSF 可能是脊髓损伤后恢复治疗的一种有前途的策略。

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