Lobeline improves acute lung injury via nuclear factor-κB-signaling pathway and oxidative stress
Lobeline improves acute lung injury via nuclear factor-κB-signaling pathway and oxidative stress
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DOI：
10.1016/j.resp.2015.12.003
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发表时间：
2016-05-01
影响因子：
2.3
通讯作者：
Huang, Guan-Jhong
中科院分区：
文献类型：
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作者：
Li, Kun-Cheng;Ho, Yu-Ling;Huang, Guan-Jhong
急性肺损伤（ALI）是一种严重的、危及生命的疾病，其发病机制与肺中性粒细胞浸润有关。中性粒细胞的活化和向肺的募集主要归因于趋化因子NO的产生，例如IL-6。本研究旨在探讨红叶碱降低NO生成和一氧化氮合酶（iNOs）表达的能力。Lobeline通过抑制lps刺激的RAW 264.7细胞中丝裂原活化蛋白激酶（MAPKs）、nf - κ B和I κ B α的磷酸化来检测。当给RAW 264.7巨噬细胞注射含有LPS的lobeline时，检测到NO产生的显著浓度依赖性抑制。在体实验中，小鼠分别腹腔注射生理盐水、10 mg/kg地米松或5、10、20 mg/kg洛比林，1小时后气管注射5 mg/kg LPS。体外表现、细胞因子、MAPK通路和抗氧化酶（AOEs）也被用来评价这些药物的作用。本研究首次发现洛贝林可有效抑制急性肺水肿，为ALI治疗提供潜在靶点。Lobeline可能利用MAPKs通路和AOEs活性来减弱lps诱导的非特异性肺部炎症。(C) 2016 Elsevier B.V.版权所有
Acute lung injury (ALI) is a severe, life-threatening medical condition whose pathogenesis is linked to neutrophil infiltration of the lung. Activation and recruitment of neutrophils to the lung is mostly attributed to the production of chemokines NO, IL-6, for instance. This study aims to investigate lobeline ability in reducing NO production, and nitric oxide synthase (iNOs) expression. Lobeline was tested by inhibiting phosphorylation of mitogen-activated protein kinases (MAPKs), NF-kappa B and I kappa B alpha in LPS-stimulated RAW 264.7 cells. When RAW 264.7 macrophages were given lobeline with LPS, a significant concentration dependent inhibition of NO production was detected. In vivo tests, mice were either treated with normal saline, 10 mg/kg dexmethasone or 5, 10, 20 mg/kg lobeline intraperitoneally, and after an hour, the administration of 5 mg/kg of LPS was given intratracheally. External performance, cytokines, MAPK pathways and antioxidative enzymes (AOEs) were also carried out to evaluate the effects of these drugs. This is the first investigation in which lobeline was found to effectively inhibit acute lung edema, which may provide a potential target for treating ALI. Lobeline may utilize MAPKs pathways as well as AOEs activity to attenuate LPS-induced nonspecific pulmonary inflammation. (C) 2016 Elsevier B.V. All rights reserved.