Hydrogen Sulfide Prevents Sleep Deprivation-Induced Hippocampal Damage by Upregulation of Sirt1 in the Hippocampus

Hydrogen Sulfide Prevents Sleep Deprivation-Induced Hippocampal Damage by Upregulation of Sirt1 in the Hippocampus
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硫化氢通过上调海马 Sirt1 来防止睡眠剥夺引起的海马损伤

DOI:
10.3389/fnins.2020.00169
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发表时间:
2020-03
影响因子:
4.3
通讯作者:
Tang Xiao-Qing
Tang Xiao-Qing
中科院分区:
医学2区
文献类型:
--
作者:
Zuo Jin-Xi;Li Min;Jiang Li;Lan Fang;Tang Yi-Yun;Kang Xuan;Zou Wei;Wang Chun-Yan;Zhang Ping;Tang Xiao-Qing

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睡眠剥夺(SD)可导致海马损伤。硫化氢(H2S)是一种神经保护因子。沉默信息调节因子1(Silence information regulating factor 1,Sirt 1)在神经保护中起重要作用。因此,本研究旨在探讨H2S是否减轻SD诱导的海马损伤以及Sirt 1是否介导H2S的这种保护作用。我们发现,硫氢化钠(NaHS,H2S的供体)减轻SD引起的海马氧化应激,包括增加SOD的激活和GSH的水平,以及在MDA的水平下降。同时,我们发现NaHS降低了SD引起的海马内质网(ER)应激,包括GRP 78,CHOP和cleaved-caspase-12表达的下调。此外,NaHS还能减少SD大鼠海马细胞凋亡,包括减少凋亡细胞数、降低caspase-3活性、下调Bax表达、上调Bcl-2表达。NaHS上调SD大鼠海马Sirt 1的表达。此外,Sirt 1的抑制剂Sirtinol废除了NaHS对SD引起的海马氧化应激、ER应激和细胞凋亡的保护。这些结果表明,H2S通过上调海马Sirt 1来减轻SD诱导的海马损伤。
Sleep deprivation (SD) induces hippocampal damage. Hydrogen sulfide (H2S) is a neuronal protective factor. Silence information regulating factor 1 (Sirt1) plays an important role in neuroprotection. Therefore, this study was aimed at exploring whether H2S meliorates SD-induced hippocampal damage and whether Sirt1 mediates this protective role of H2S. We found that sodium hydrosulfide (NaHS, a donor of H2S) alleviated SD-generated hippocampal oxidative stress, including increases in the activation of SOD and the level of GSH as well as a decrease in the level of MDA. Meanwhile, we found that NaHS reduced SD-exerted hippocampal endoplasmic reticulum (ER) Stress, including downregulations of GRP78, CHOP, and cleaved-caspase-12 expression. Moreover, NaHS reduced the apoptosis in the SD-exposed hippocampus, and this included decreases in the number of apoptotic cells and the activation of caspase-3, downregulation of Bax expression, and upregulation of Bcl-2 expression. NaHS upregulated the expression of Sirt1 in the hippocampus of SD-exposed rats. Furthermore, Sirtinol, the inhibitor of Sirt1, abrogated the protection of NaHS against SD-exerted hippocampal oxidative stress, ER stress, and apoptosis. These results suggested that H2S alleviates SD-induced hippocampal damage by upregulation of hippocampal Sirt1.
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