Hydrogen sulfide attenuates hypoxia-induced neurotoxicity through inhibiting microglial activation
Hydrogen sulfide attenuates hypoxia-induced neurotoxicity through inhibiting microglial activation
复制标题
硫化氢通过抑制小胶质细胞活化减轻缺氧引起的神经毒性
DOI：
10.1016/j.phrs.2014.04.009
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发表时间：
2014-06-01
影响因子：
9.3
通讯作者：
Wang, Zhen
中科院分区：
文献类型：
--
作者：
Zhang, Qun;Yuan, Lin;Wang, Zhen
内源性产生的硫化氢（H2S）可能在大脑中具有多种功能，包括有效的抗炎作用。活化的小胶质细胞可以分泌多种促炎细胞因子和神经毒性介质，这可能有助于发育中脑的缺氧损伤。本研究的目的是探讨H2S通过其抗炎作用在体外和体内模型中改变缺氧诱导的神经毒性的潜在作用。使用BV-2小胶质细胞系，我们发现，硫氢化钠（NaHS），H2S供体，显着抑制缺氧诱导的小胶质细胞活化，并抑制随后的促炎因子释放。此外，用来自缺氧刺激的小胶质细胞的条件培养基（CM）处理小鼠原代皮层神经元诱导神经元凋亡，这种作用被用NaHS处理的CM逆转。此外，NaHS抑制这些缺氧诱导的小胶质细胞中NF-κ B B的p65亚基的磷酸化，ERK和p38的磷酸化，但不抑制JNK MAPK。当在体内给药的新生小鼠缺氧，NaHS被发现减弱神经元死亡，与抑制小胶质细胞活化，促炎细胞因子和NO水平的影响。总之，H2S通过其在小胶质细胞中的抗炎作用对缺氧诱导的神经毒性发挥神经保护作用。这种作用似乎可归因于iNOS、NF-κ B、ERK和p38 MAPK信号通路的抑制。我们的结果表明释放H2S的药物在缺氧性脑损伤治疗中具有潜在的治疗应用。(C)2014爱思唯尔有限公司版权所有。
Endogenously produced hydrogen sulfide (H2S) may have multiple functions in the brain including potent anti-inflammatory effects. Activated microglia can secrete various pro-inflammatory cytokines and neurotoxic mediators, which may contribute to hypoxic injuries in the developing brain. The aim of this study is to investigate the potential role of H2S in altering hypoxia-induced neurotoxicity via its anti-inflammatory actions as examined in vitro and in vivo models. Using the BV-2 microglial cell line, we found that sodium hydrosulfide (NaHS), a H2S donor, significantly inhibited hypoxia-induced microglial activation and suppressed subsequent pro-inflammatory factor release. In addition, treating murine primary cortical neurons with conditioned medium (CM) from hypoxia-stimulated microglia induced neuronal apoptosis, an effect that was reversed by CM treated with NaHS. Further, NaHS inhibited phosphorylation of the p65 subunit of NF-kappa B, phosphorylation of ERK and p38 but not JNK MAPK in these hypoxia-induced microglia. When administered in vivo to neonatal mice subjected to hypoxia, NaHS was found to attenuate neuron death, an effect that was associated with suppressed microglial activation, pro-inflammatory cytokines and NO levels. Taken together, H2S exerts neuroprotection against hypoxia-induced neurotoxicity through its anti-inflammatory effect in microglia. This effect appears to be attributable to inhibition of iNOS, NF-kappa B, ERK and p38 MAPK signaling pathways. Our results suggest a potential therapeutic application of H2S releasing drugs in hypoxic brain damage treatment. (C) 2014 Elsevier Ltd. All rights reserved.