Naloxone Protects against Lipopolysaccharide-Induced Neuroinflammation and Microglial Activation via Inhibiting ATP-Sensitive Potassium Channel.
Naloxone Protects against Lipopolysaccharide-Induced Neuroinflammation and Microglial Activation via Inhibiting ATP-Sensitive Potassium Channel.
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纳洛酮通过抑制 ATP 敏感钾通道来防止脂多糖诱导的神经炎症和小胶质细胞活化
DOI：
10.1155/2021/7731528
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发表时间：
2021
影响因子：
--
通讯作者：
Yuan B
中科院分区：
文献类型：
--
作者：
Tang Z;Shao X;Wu J;Chen H;Zhang A;Xu F;Ping H;Li S;Liu C;Li Y;Xue X;Yuan B
目的探讨纳洛酮对脂多糖（LPS）诱导的神经元炎症和小胶质细胞活化的抗炎作用及其机制。方法采用LPS诱导的BV-2小胶质细胞和小鼠模型，观察纳洛酮的抗炎作用。结果纳洛酮剂量依赖性地促进LPS诱导的BV-2细胞增殖，下调LPS诱导的BV-2细胞和小鼠脑组织中促炎细胞因子TNF-α、IL-1β和IL-6、促炎酶iNOS和考克斯-2的表达以及自由基分子NO的表达，减少Iba-1阳性小胶质细胞的表达。此外，纳洛酮改善LPS诱导的小鼠行为退化。在机械上，纳洛酮抑制LPS诱导的ATP敏感性钾（KATP）通道激活。然而，存在格列本脲（Glib），KATP通道拮抗剂，改善纳洛酮对炎症和小胶质细胞活化的抑制作用。结论纳洛酮部分通过KATP通道抑制LPS诱导的神经炎症和小胶质细胞活化。这些发现可能突出了纳洛酮在神经炎症治疗中的潜力。
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-α, IL-1β, 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.
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影响因子：
5.3
作者：
Ortega, F. J.;Gimeno-Bayon, J.;Rodriguez, M. J.
通讯作者：
Rodriguez, M. J.
影响因子：
25
作者：
Schiemann, Julia;Schlaudraff, Falk;Klose, Verena;Bingmer, Markus;Seino, Susumu;Magill, Peter J.;Zaghloul, Kareem A.;Schneider, Gaby;Liss, Birgit;Roeper, Jochen
通讯作者：
Roeper, Jochen
DOI：
10.1124/jpet.102.035048
发表时间：
2003-01-01
影响因子：
3.5
作者：
Liu, B;Hong, JS
通讯作者：
Hong, JS
影响因子：
5
作者：
Stoller, Douglas;Kakkar, Rahul;McNally, Elizabeth M.
通讯作者：
McNally, Elizabeth M.
影响因子：
1.8
作者：
Tian, Ji-Sha;Zhai, Qi-Jin;Zhao, Lian-Dong
通讯作者：
Zhao, Lian-Dong