纳洛酮通过抑制三磷酸腺苷敏感性钾通道保护脂多糖诱导的神经炎症和小胶质细胞激活。
Naloxone Protects against Lipopolysaccharide-Induced Neuroinflammation and Microglial Activation via Inhibiting ATP-Sensitive Potassium Channel.
机构信息
Department of Medicine, Tongling Technology College, Anhui 244061, China.
Department of Transfusion Medicine, The Affiliated Nanjing Traditional Chinese Medicine Hospital, Nanjing University of Chinese Medicine, Nanjing 210022, China.
出版信息
Comput Math Methods Med. 2021 Jul 29;2021:7731528. doi: 10.1155/2021/7731528. eCollection 2021.
AIM
The aim of this study was to evaluate the anti-inflammatory effects and underlying mechanism of naloxone on lipopolysaccharide- (LPS-) induced neuronal inflammation and microglial activation.
METHODS
LPS-treated microglial BV-2 cells and mice were used to investigate the anti-inflammatory effects of naloxone.
RESULTS
The results showed that naloxone dose-dependently promoted cell proliferation in LPS-induced BV-2 cells, downregulated the expression of proinflammatory cytokines (TNF-, IL-1, and IL-6) and proinflammatory enzymes iNOS and COX-2 as well as the expression of free radical molecule NO, and reduced the expression of Iba-1-positive microglia in LPS-stimulated BV-2 cells and mouse brain. Moreover, naloxone improved LPS-induced behavior degeneration in mice. Mechanically, naloxone inhibited LPS-induced activation in the ATP-sensitive potassium (KATP) channel. However, the presence of glibenclamide (Glib), an antagonist of KATP channel, ameliorated the suppressive effects of naloxone on inflammation and microglial activation.
CONCLUSION
Naloxone prevented LPS-induced neuroinflammation and microglial activation partially through the KATP channel. These findings might highlight the potential of naloxone in neuroinflammation therapy.
目的
本研究旨在评估纳洛酮对脂多糖（LPS）诱导的神经元炎症和小胶质细胞激活的抗炎作用及其机制。
方法
采用 LPS 处理的小胶质细胞 BV-2 细胞和小鼠来研究纳洛酮的抗炎作用。
结果
结果表明，纳洛酮呈剂量依赖性促进 LPS 诱导的 BV-2 细胞增殖，下调促炎细胞因子（TNF-α、IL-1 和 IL-6）和促炎酶 iNOS 和 COX-2 以及自由基分子 NO 的表达，并减少 LPS 刺激的 BV-2 细胞和小鼠大脑中 Iba-1 阳性小胶质细胞的表达。此外，纳洛酮改善了 LPS 诱导的小鼠行为退化。在机制上，纳洛酮抑制了 LPS 诱导的三磷酸腺苷（ATP）敏感性钾（KATP）通道的激活。然而，KATP 通道拮抗剂格列本脲（Glib）的存在改善了纳洛酮对炎症和小胶质细胞激活的抑制作用。
结论
纳洛酮通过 KATP 通道部分预防 LPS 诱导的神经炎症和小胶质细胞激活。这些发现可能突出了纳洛酮在神经炎症治疗中的潜力。
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