Department of Neurology, The first affiliated hospital of China Medical University, Shenyang, China; Department of Neurology, The first affiliated hospital of Dalian Medical University, Dalian, China.
Department of Neurology, The first affiliated hospital of China Medical University, Shenyang, China.
Neurosci Lett. 2019 Oct 15;711:134387. doi: 10.1016/j.neulet.2019.134387. Epub 2019 Jul 19.
Accumulating evidence has shown that astrocytes play a critical role in neuroinflammation and protection against oxidative stress. In this study, we investigated the effects of sigma-1 receptor (Sig-1R) activation on lipopolysaccharide (LPS)-induced inflammatory reactions and oxidative/nitrosative stress in cultured astrocytes. We found that SA4503, a selective Sig-1R agonist, attenuated LPS-induced inflammatory reactions and oxidative/nitrosative stress by downregulating the expression of iNOS and tumor necrosis factor α (TNF-α) and upregulating glutathione (GSH) in cultured astrocytes. To investigate the mechanism by which SA4503 caused these effects, we then examined the expression of nuclear factor erythroid-derived 2-like 2 (Nrf2) and heme oxygenase-1 (HO-1) through western blotting. The results revealed that SA4503 treatment increased Nrf2 and HO-1 expression significantly. These results suggested that the antioxidative/nitrosative stress and anti-inflammatory effects of Sig-1R activation in astrocytes were partially mediated by Nrf2 and HO-1 activation.
越来越多的证据表明星形胶质细胞在神经炎症和抵抗氧化应激中起着关键作用。在这项研究中，我们研究了 sigma-1 受体 (Sig-1R) 激活对培养的星形胶质细胞中脂多糖 (LPS) 诱导的炎症反应和氧化/硝化应激的影响。我们发现，选择性 Sig-1R 激动剂 SA4503 通过下调诱导型一氧化氮合酶 (iNOS) 和肿瘤坏死因子 α (TNF-α) 的表达以及上调谷胱甘肽 (GSH) 的表达，减轻了 LPS 诱导的炎症反应和氧化/硝化应激。为了研究 SA4503 引起这些作用的机制，我们通过 Western blot 检测了核因子红细胞衍生 2 样 2 (Nrf2) 和血红素加氧酶-1 (HO-1) 的表达。结果表明，SA4503 处理显著增加了 Nrf2 和 HO-1 的表达。这些结果表明，星形胶质细胞中 Sig-1R 激活的抗氧化/硝化应激和抗炎作用部分是通过 Nrf2 和 HO-1 的激活介导的。
