Zinc Improves Functional Recovery by Regulating the Secretion of Granulocyte Colony Stimulating Factor From Microglia/Macrophages After Spinal Cord Injury
Zinc Improves Functional Recovery by Regulating the Secretion of Granulocyte Colony Stimulating Factor From Microglia/Macrophages After Spinal Cord Injury
复制标题
锌通过调节脊髓损伤后小胶质细胞/巨噬细胞分泌粒细胞集落刺激因子来改善功能恢复
DOI：
10.3389/fnmol.2019.00018
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发表时间：
2019-02-01
影响因子：
4.8
通讯作者：
Mei, Xifan
中科院分区：
文献类型：
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作者：
Li, Xian;Chen, Shurui;Mei, Xifan
虽然锌促进脊髓损伤（SCI）后的运动功能恢复，但所涉及的确切机制尚未完全了解。本研究旨在阐明锌和粒细胞集落刺激因子（G-CSF）对脊髓损伤后神经元恢复的影响。采用艾伦法建立脊髓损伤模型。伤后2 h首次给予葡萄糖和葡萄糖酸锌（ZnG; 30 mg/kg），连续3d。细胞因子抗体阵列用于筛选SCI损伤部位的炎症变化。免疫荧光法检测细胞因子的分布。磁珠也被用于从SCI损伤部位分离细胞。然后，我们研究了锌对脊髓损伤后细胞凋亡的影响，转移酶UTP缺口末端标记（TUNEL）染色和Western印迹。采用Basso小鼠量表（BMS）评分和免疫荧光法研究神经元凋亡和功能恢复。我们发现，锌的管理显着增加了19个细胞因子在SCI病变的表达。其中，G-CSF被证明是最升高的细胞因子，并且在SCI后通过核因子-κ B（NF-κB）信号通路由小胶质细胞/巨噬细胞（M/Ms）分泌。SCI损伤处G-CSF水平的增加降低了SCI后神经元凋亡的水平，从而促进功能恢复。总的来说，我们的研究结果表明，锌的管理增加了M/MS分泌的G-CSF的表达，从而导致SCI后神经元凋亡水平降低。
While zinc promotes motor function recovery after spinal cord injury (SCI), the precise mechanisms involved are not fully understood. The present study aimed to elucidate the effects of zinc and granulocyte colony stimulating factor (G-CSF) on neuronal recovery after SCI. The SCI model was established by Allen’s method. Injured animals were given glucose and zinc gluconate (ZnG; 30 mg/kg) for the first time at 2 h after injury, the same dose was given for 3 days. A cytokine antibody array was used to screen changes in inflammation at the site of SCI lesion. Immunofluorescence was used to detect the distribution of cytokines. Magnetic beads were also used to isolate cells from the site of SCI lesion. We then investigated the effect of Zinc on apoptosis after SCI by Transferase UTP Nick End Labeling (TUNEL) staining and Western Blotting. Basso Mouse Scale (BMS) scores and immunofluorescence were employed to investigate neuronal apoptosis and functional recovery. We found that the administration of zinc significantly increased the expression of 19 cytokines in the SCI lesion. Of these, G-CSF was shown to be the most elevated cytokine and was secreted by microglia/macrophages (M/Ms) via the nuclear factor-kappa B (NF-κB) signaling pathway after SCI. Increased levels of G-CSF at the SCI lesion reduced the level of neuronal apoptosis after SCI, thus promoting functional recovery. Collectively, our results indicate that the administration of zinc increases the expression of G-CSF secreted by M/Ms, which then leads to reduced levels of neuronal apoptosis after SCI.