Gua Lou Gui Zhi decoction suppresses LPS-induced activation of the TLR4/NF-κB pathway in BV-2 murine microglial cells
Gua Lou Gui Zhi decoction suppresses LPS-induced activation of the TLR4/NF-κB pathway in BV-2 murine microglial cells
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DOI：
10.3892/ijmm.2013.1331
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发表时间：
2013-06-01
影响因子：
5.4
通讯作者：
Chen, Lidian
中科院分区：
文献类型：
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作者：
Hu, Haixia;Li, Zuanfang;Chen, Lidian
Toll样受体4（TLR 4）/核因子-κ B（NF-kappa B）信号通路介导的神经炎症导致缺血性卒中继发性脑损伤;因此，通过抑制TLR 4/NF-kappa B通路进行抗炎治疗可能是治疗卒中和卒中后残疾的有希望的策略。瓜蒌桂枝汤（GLGZD）长期以来在中国临床上用于治疗中风后功能障碍，如肌痉挛，但确切的机制在很大程度上是未知的。在本研究中，我们评估了GLGZD的抗炎作用，并研究了潜在的分子机制，使用脂多糖（LPS）刺激的BV-2小胶质细胞作为神经细胞的体外炎症模型。我们发现GLGZD抑制小胶质细胞的炎症反应，因为它以剂量依赖性方式显著降低BV-2细胞中LPS诱导的促炎性一氧化氮、肿瘤坏死因子-α、白细胞介素（IL）-6和IL-1 β的表达。此外，GLGZD还能显著降低BV-2细胞中TLR 4和髓样分化因子88的蛋白表达，抑制I kappa B的磷酸化，阻断NF-κ B的核转位，从而抑制TLR 4/NF-κ B信号通路的激活。总之，我们的研究结果表明，通过抑制TLR 4/NF-κ B通路抑制炎症反应可能是GLGZD改善缺血性脑组织损伤的机制之一。
Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-kappa B) signaling-mediated neuroinflammation contributes to secondary brain damage in ischemic stroke; therefore, anti-inflammatory therapy via suppression of the TLR4/NF-kappa B pathway could be a promising strategy for the treatment of stroke and post-stroke disabilities. Gua Lou Gui Zhi decoction (GLGZD) has long been used in China to clinically treat dysfunction after stroke such as muscular spasticity, but the precise mechanisms are largely unknown. In the present study, we evaluated the anti-inflammatory effect of GLGZD and investigated the underlying molecular mechanisms using lipopolysaccharide (LPS)-stimulated BV-2 microglial cells as an in vitro inflammatory model of neural cells. We found that GLGZD inhibited the inflammatory response in microglial cells as it significantly reduced LPS-induced expression of pro-inflammatory nitric oxide, tumour necrosis factor-alpha, interleukin (IL)-6 and IL-1 beta in BV-2 cells, in a dose-dependent manner. In addition, GLGZD treatment significantly decreased the protein expression of TLR4 and myeloid differentiation factor 88, inhibited the phosphorylation of I kappa B and blocked the nuclear translocation of NF-kappa B in BV-2 cells, demonstrating its inhibitory effect on the activation of TLR4/NF-kappa B signaling. Collectively, our findings suggest that inhibition of the inflammatory response via suppression of the TLR4/NF-kappa B pathway may be one of the mechanisms through which GLGZD ameliorates the damage in ischemic cerebral tissues.