Hydrogen Sulfide Protects against Chronic Unpredictable Mild Stress-Induced Oxidative Stress in Hippocampus by Upregulation of BDNF-TrkB Pathway.
Hydrogen Sulfide Protects against Chronic Unpredictable Mild Stress-Induced Oxidative Stress in Hippocampus by Upregulation of BDNF-TrkB Pathway.
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硫化氢通过上调 BDNF-TrkB 通路来保护海马免受慢性不可预测的轻度应激诱导的氧化应激
DOI：
10.1155/2016/2153745
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发表时间：
2016
影响因子：
--
通讯作者：
Tang XQ
中科院分区：
文献类型：
--
作者：
Hu M;Zou W;Wang CY;Chen X;Tan HY;Zeng HY;Zhang P;Gu HF;Tang XQ
慢性不可预测的轻度应激(CUMS)可诱导海马区氧化应激。硫化氢在大脑中起着神经保护剂的作用，防止氧化应激。我们先前已经证明了硫化氢对大鼠海马区BDNF蛋白表达的上调作用。因此，我们假设H_2S通过上调BDNF-TrkB途径来抑制CUMS产生的氧化应激。结果表明，NaHS(0.03或0.1NaHS/ /kg/d)可明显减轻海马区氧化应激水平，降低丙二醛和4-羟基-2-反式-壬烯醛水平，提高谷胱甘肽水平和超氧化物歧化酶活性。我们还发现，硫化氢可上调CUMS大鼠海马区BDNF和p-TrkB蛋白的表达。此外，BDNF受体TrkB的抑制剂K252a对BDNF信号的抑制可阻断硫化氢对CUMS诱导的海马区氧化应激的抗氧化作用。这些结果揭示了硫化氢在CUMS诱导的海马区氧化应激中的抑制作用，这可能是通过上调BDNF/TrkB途径实现的。
Chronic unpredictable mild stress (CUMS) induces hippocampal oxidative stress. H2S functions as a neuroprotectant against oxidative stress in brain. We have previously shown the upregulatory effect of H2S on BDNF protein expression in the hippocampus of rats. Therefore, we hypothesized that H2S prevents CUMS-generated oxidative stress by upregulation of BDNF-TrkB pathway. We showed that NaHS (0.03 or 0.1 mmol/kg/day) ameliorates the level of hippocampal oxidative stress, including reduced levels of malondialdehyde (MDA) and 4-hydroxy-2-trans-nonenal (4-HNE), as well as increased level of glutathione (GSH) and activity of superoxide dismutase (SOD) in the hippocampus of CUMS-treated rats. We also found that H2S upregulated the level of BDNF and p-TrkB protein in the hippocampus of CUMS rats. Furthermore, inhibition of BDNF signaling by K252a, an inhibitor of the BDNF receptor TrkB, blocked the antioxidant effects of H2S on CUMS-induced hippocampal oxidative stress. These results reveal the inhibitory role of H2S in CUMS-induced hippocampal oxidative stress, which is through upregulation of BDNF/TrkB pathway.