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一种绿茶多酚表没食子儿茶素没食子酸酯通过改变炎症细胞因子的水平增强脊髓损伤后的神经再生。

A green tea polyphenol epigallocatechin-3-gallate enhances neuroregeneration after spinal cord injury by altering levels of inflammatory cytokines.

机构信息

Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Vídeňská 1083, Prague, Czech Republic.

Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Vídeňská 1083, Prague, Czech Republic; Department of Neuroscience, Charles University, Second Faculty of Medicine, Prague, Czech Republic.

出版信息

Neuropharmacology. 2017 Nov;126:213-223. doi: 10.1016/j.neuropharm.2017.09.006. Epub 2017 Sep 9.

Abstract

Spinal cord injury (SCI) is a debilitating condition which is characterized by an extended secondary injury due to the presence of inflammatory local milieu. Epigallocatechin gallate (EGCG) appears to possess strong neuroprotective properties. Here, we evaluated the beneficial effect of EGCG on recovery from SCI. Male Wistar rats were given either EGCG or saline directly to the injured spinal cord and thereafter a daily IP injection. Behavior recovery was monitored by BBB, plantar, rotarod and flat-beam tests. The levels of inflammatory cytokines were determined on days 1, 3, 7, 10 and 14 after SCI. Additionally, NF-κB pathway activity was evaluated. The results demonstrated that EGCG-treated rats displayed a superior behavioral performance in a flat beam test, higher axonal sprouting and positive remodelation of glial scar. Cytokine analysis revealed a reduction in IL-6, IL2, MIP1α and RANTES levels on days 1 and 3, and an upregulation of IL-4, IL-12p70 and TNFα 1 day following SCI in EGCG-treated rats. Treatment with EGCG was effective in decreasing the nuclear translocation of subunit p65 (RelA) of the NF-κB dimer, and therefore canonical NF-κB pathway attenuation. A significant increase in the gene expression of growth factors (FGF2 and VEGF), was noted in the spinal cord of EGCG-treated rats. Further, EGCG influenced expression of M1 and M2 macrophage markers. Our results have demonstrated a therapeutic value of EGCG in SCI, as observed by better behavioral performance measured by flat beam test, modulation of inflammatory cytokines and induction of higher axonal sprouting.

摘要

脊髓损伤(SCI)是一种使人虚弱的疾病,其特征是由于炎症局部环境的存在,导致继发性损伤延长。表没食子儿茶素没食子酸酯(EGCG)似乎具有很强的神经保护特性。在这里,我们评估了 EGCG 对 SCI 恢复的有益影响。雄性 Wistar 大鼠直接给予 EGCG 或生理盐水至受伤的脊髓,然后每天进行 IP 注射。通过 BBB、足底、转棒和扁平梁试验监测行为恢复。在 SCI 后第 1、3、7、10 和 14 天测定炎症细胞因子水平。此外,还评估了 NF-κB 途径的活性。结果表明,在扁平梁试验中,EGCG 处理的大鼠表现出更好的行为表现,轴突发芽更多,神经胶质瘢痕的正性重塑。细胞因子分析显示,在 SCI 后第 1 和 3 天,IL-6、IL2、MIP1α 和 RANTES 水平降低,在 SCI 后第 1 天,IL-4、IL-12p70 和 TNFα 水平上调。EGCG 治疗可有效降低 NF-κB 二聚体亚基 p65(RelA)的核易位,从而抑制经典 NF-κB 途径。在 EGCG 处理的大鼠脊髓中,生长因子(FGF2 和 VEGF)的基因表达显著增加。此外,EGCG 还影响 M1 和 M2 巨噬细胞标志物的表达。我们的研究结果表明,EGCG 在 SCI 中具有治疗价值,这可以通过扁平梁试验更好的行为表现、炎症细胞因子的调节和更高的轴突发芽来衡量。

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