红景天苷通过调节脑缺血后小胶质细胞极化发挥神经保护作用。
Salidroside provides neuroprotection by modulating microglial polarization after cerebral ischemia.
机构信息
China-America Institute of Neuroscience, Xuanwu Hospital of Capital Medical University, Beijing, 100053, People's Republic of China.
Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, 100053, People's Republic of China.
出版信息
J Neuroinflammation. 2018 Feb 9;15(1):39. doi: 10.1186/s12974-018-1081-0.
BACKGROUND
Following stroke, microglia can be driven to the "classically activated" pro-inflammatory (M1) phenotype and the "alternatively activated" anti-inflammatory (M2) phenotype. Salidroside (SLDS) is known to inhibit inflammation and to possess protective effects in neurological diseases, but to date, the exact mechanisms involved in these processes after stroke have yet to be elucidated. The purpose of this study was to determine the effects of SLDS on neuroprotection and microglial polarization after stroke.
METHODS
Male adult C57/BL6 mice were subjected to focal transient cerebral ischemia followed by intravenous SLDS injection. The optimal dose was determined by evaluation of cerebral infarct volume and neurological functions. RT-PCR and immunostaining were performed to assess microglial polarization. A transwell system and a direct-contact coculture system were used to elucidate the effects of SLDS-induced microglial polarization on oligodendrocyte differentiation and neuronal survival.
RESULTS
SLDS significantly reduced cerebral infarction and improved neurological function after cerebral ischemia. SLDS treatment reduced the expression of M1 microglia/macrophage markers and increased the expression of M2 microglia/macrophage markers after stroke and induced primary microglia from M1 phenotype to M2 phenotype. Furthermore, SLDS treatment enhanced microglial phagocytosis and suppressed microglial-derived inflammatory cytokine release. Cocultures of oligodendrocytes and SLDS-treated M1 microglia resulted in increased oligodendrocyte differentiation. Moreover, SLDS protected neurons against oxygen glucose deprivation by promoting microglial M2 polarization.
CONCLUSIONS
These data demonstrate that SLDS protects against cerebral ischemia by modulating microglial polarization. An understanding of the mechanisms involved in SLDS-mediated microglial polarization may lead to new therapeutic opportunities after stroke.
背景
中风后，小胶质细胞可被诱导向经典激活的促炎（M1）表型和替代激活的抗炎（M2）表型极化。红景天苷（SLDS）已知具有抑制炎症和在神经疾病中具有保护作用，但迄今为止，其在中风后发挥这些作用的确切机制仍未阐明。本研究旨在确定 SLDS 对中风后神经保护和小胶质细胞极化的影响。
方法
雄性成年 C57/BL6 小鼠接受局灶性短暂性脑缺血，随后静脉注射 SLDS。通过评估脑梗死体积和神经功能来确定最佳剂量。通过 RT-PCR 和免疫染色来评估小胶质细胞极化。使用 Transwell 系统和直接接触共培养系统来阐明 SLDS 诱导的小胶质细胞极化对少突胶质细胞分化和神经元存活的影响。
结果
SLDS 可显著减少脑缺血后的脑梗死并改善神经功能。SLDS 治疗可降低中风后 M1 小胶质细胞/巨噬细胞标志物的表达，增加 M2 小胶质细胞/巨噬细胞标志物的表达，并诱导原代小胶质细胞从 M1 表型向 M2 表型转化。此外，SLDS 治疗增强了小胶质细胞的吞噬作用并抑制了小胶质细胞衍生的炎症细胞因子释放。与 SLDS 处理的 M1 小胶质细胞共培养可增加少突胶质细胞分化。此外，SLDS 通过促进小胶质细胞 M2 极化来保护神经元免受氧葡萄糖剥夺。
结论
这些数据表明，SLDS 通过调节小胶质细胞极化来保护大脑免受缺血损伤。对 SLDS 介导的小胶质细胞极化相关机制的理解可能为中风后提供新的治疗机会。
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