孟鲁司特抑制呼吸道合胞病毒感染人支气管上皮细胞所致炎症的药理机制

发布时间：2019-02-28 12:49

【摘要】：【目的】探讨孟鲁司特抑制炎症过程中的药理机制。【方法】构建呼吸道合胞病毒感染人支气管上皮细胞(16HBEC)炎症模型,分别用qPCR和Western-blot方法检测核因子NF-E2相关因子(Nrf2)、血红素加氧酶1(HO-1)、醌氧化还原酶1(NQO-1)、谷胱甘肽硫转移酶(GST)的mRNA水平和蛋白水平,荧光探针DCFH-DA法检测细胞活性氧化物(ROS)的产生。进一步通过合成Nrf2小干扰RNA(Nrf2 siRNA),下调Nrf2的表达后,探究炎症指标的变化情况。【结果】孟鲁司特显著降低RSV感染后炎症因子IL-6、TNF-α和IL-1β的表达(P0.05)及细胞中ROS水平(P0.05),增加细胞炎症模型中Nrf2、HO-1、NQO-1、GST的基因与蛋白表达(P0.05),且高剂量的孟鲁司特效果越显著。下调Nrf2的表达后,炎症因子IL-6、TNF-α和IL-1β表达量上升(P0.05)及活性氧ROS含量明显升高(P0.05),Nrf2、HO-1、NQO-1、GST的基因与蛋白表达量下降(P0.05)。【结论】孟鲁司特能抑制呼吸道合胞病毒感染人支气管上皮细胞所致的炎症,其作用机制可能是影响Nrf2/ARE信号通路。
[Abstract]:[objective] to investigate the pharmacological mechanism of montelukast in inhibiting inflammation. [methods] to establish a model of respiratory syncytial virus infection in human bronchial epithelial cells (16HBEC). The levels of mRNA and protein of nuclear factor NF-E2 associated factor (Nrf2), heme oxygenase 1 (HO-1), quinone oxidoreductase 1 (NQO-1) and glutathione S transferase (GST) (GST) were detected by qPCR and Western-blot, respectively. Fluorescence probe DCFH-DA was used to detect the production of (ROS). Furthermore, through the synthesis of Nrf2 small interfering RNA (Nrf2 siRNA), down-regulated the expression of Nrf2), to explore the changes of inflammatory markers. [results] Montelukast significantly decreased the inflammatory factor IL-6, after RSV infection. The expression of TNF- 伪 and IL-1 尾 (P0.05) and the level of ROS in cells (P0.05) increased the expression of Nrf2,HO-1,NQO-1,GST gene and protein in inflammatory cell model (P0.05), and the higher the dose of montelukast, the more significant the effect was. After down regulating the expression of Nrf2, the expression of inflammatory factors IL-6,TNF- 伪 and IL-1 尾 was increased (P0.05) and the content of reactive oxygen species (ROS) was significantly increased (P0.05), and Nrf2,HO-1,NQO-1, was significantly increased (P0.05). [conclusion] Montelukast can inhibit the inflammation induced by respiratory syncytial virus infection in human bronchial epithelial cells, the mechanism of which may be to affect the Nrf2/ARE signaling pathway. [conclusion] Montelukast can inhibit the inflammation induced by respiratory syncytial virus infection in human bronchial epithelial cells (GST) (P0.05).
【作者单位】：广州市中西医结合医院;中山大学孙逸仙纪念医院;
【基金】：广东省医学科研基金(B2013120)
【分类号】：R96

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