Hydrogen Alleviates Neuronal Injury and Neuroinflammation Induced by Microglial Activation via the Nuclear Factor Erythroid 2-related Factor 2 Pathway in Sepsis-associated Encephalopathy
Hydrogen Alleviates Neuronal Injury and Neuroinflammation Induced by Microglial Activation via the Nuclear Factor Erythroid 2-related Factor 2 Pathway in Sepsis-associated Encephalopathy
复制标题
氢气可减轻脓毒症相关脑病中小胶质细胞通过核因子红细胞 2 相关因子 2 通路激活引起的神经元损伤和神经炎症
DOI：
10.1016/j.neuroscience.2021.05.003
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发表时间：
2021-05-28
期刊：
影响因子：
3.3
通讯作者：
Xie, Keliang
中科院分区：
文献类型：
--
作者：
Chen, Hongguang;Dong, Beibei;Xie, Keliang
脓毒症相关脑病（SAE）的特征是弥漫性脑和中枢神经系统（CNS）功能障碍。小胶质细胞在保护脑免受神经元损伤中起着至关重要的作用，这与炎症反应密切相关。核因子红细胞2相关因子2（Nrf 2）信号通路对小胶质细胞和神经元损伤有影响。本文主要探讨了氢（H-2）调节SAE神经炎症的分子机制以及Nrf 2在此过程中的作用。通过盲肠结扎和穿刺（CLP）产生SAE的体内模型。培养原代小胶质细胞和神经元，建立体外模型。取小胶质细胞、神经元和脑组织，检测Nrf 2表达、炎症、细胞损伤、凋亡和小胶质细胞极化。测量逃避潜伏期、跨越平台的次数和在目标象限中花费的时间以评估认知功能。H-2减弱了小胶质细胞从M1到M2表型的极化、细胞因子释放和TLR/NF-κ B活化，并通过Nrf 2途径保护神经元免受脂多糖（LPS）激活的小胶质细胞诱导的损伤。SAE激活了Nrf 2表达，H-2进一步提高了SAE小鼠中的Nrf 2表达。H-2减轻了SAE小鼠和野生型小鼠中从M1到M2表型的小胶质细胞极化和大脑皮质中的细胞因子释放，并改善了神经元损伤或认知功能障碍，但在Nrf 2-/-小鼠中没有。H-2通过抑制促炎细胞因子的过度释放、神经元损失和凋亡，在体外和体内通过Nrf 2途径发挥与TLR 4/NF-κ B信号激活相关的抗神经炎性作用和神经保护作用。(C)2021年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Sepsis-associated encephalopathy (SAE) is characterized by diffuse cerebral and central nervous system (CNS) dysfunction. Microglia play a vital role in protecting the brain from neuronal damage, which is closely related to inflammatory responses. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway has an impact on microglial and neuronal injury. Here, we mainly explored the molecular mechanism by which Hydrogen (H-2) regulates neuroinflammation in SAE and the role of Nrf2 in this process. An in vivo model of SAE was generated by cecal ligation and puncture (CLP). Primary microglia and neurons were cultured to establish an in vitro model. Microglia, neurons and brain tissue were obtained to detect Nrf2 expression, inflammation, cell injury, apoptosis, and microglial polarization. Escape latency, the number of platform crossings and the time spent in the target quadrant were measured to assess cognitive function. H-2 attenuated microglial polarization from the M1 to the M2 phenotype, cytokine release and TLR/NF-kappa b activation and protected neurons from lipopolysaccharide (LPS)-activated microglia-induced injury via the Nrf2 pathway. SAE activated Nrf2 expression, and H-2 further improved Nrf2 expression in SAE mice. H-2 alleviated microglial polarization from the M1 to the M2 phenotype and cytokine release in the cerebral cortex and improved neuronal injury or cognitive dysfunction in SAE mice and wild-type mice but not in Nrf2-/- mice. H-2 exerts antineuroinflammatory effects associated with TLR4/NF-kappa B signaling activation and neuroprotective effects by inhibiting the excessive release of proinflammatory cytokines, neuronal loss and apoptosis in vitro and in vivo through the Nrf2 pathway. (C) 2021 IBRO. Published by Elsevier Ltd. All rights reserved.