The effect of magnolol on the toll-like receptor 4/nuclear factor kappa B signaling pathway in lipopolysaccharide-induced acute lung injury in mice
The effect of magnolol on the toll-like receptor 4/nuclear factor kappa B signaling pathway in lipopolysaccharide-induced acute lung injury in mice
复制标题
厚朴酚对脂多糖所致小鼠急性肺损伤中Toll样受体4/核因子κB信号通路的影响
DOI：
10.1016/j.ejphar.2012.05.038
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发表时间：
2012-08-15
影响因子：
5
通讯作者：
Yang Zhengtao
中科院分区：
文献类型：
--
作者：
Fu Yunhe;Liu Bo;Yang Zhengtao
厚朴酚是一种从厚朴中分离的羟基化联苯化合物，据报道具有抗炎特性。观察厚朴酚对脂多糖诱导的小鼠急性肺损伤的影响。雄性BALB/c小鼠在鼻内滴入脂多糖（LPS）前1h用地塞米松或厚朴酚预处理。给药后7 h，测定肺组织髓过氧化物酶、肺湿/干重比和支气管肺泡灌洗液中炎性细胞的含量。采用酶联免疫吸附试验（ELISA）检测支气管肺泡灌洗液中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1 β（IL-1 β）的水平。Western blot检测细胞核抑制因子-κ B α（I kappa B-alpha）、核因子-κ B（NF-κ B）p65的磷酸化程度及Toll样受体4（TLR 4）的表达。结果表明，厚朴酚可明显减轻肺组织病理学改变，降低支气管肺泡灌洗液中细胞总数、中性粒细胞和巨噬细胞数量，降低肺湿/干重比，下调TNF-α、IL-1 β和IL-6等促炎介质的水平，降低肺组织病理学改变。抑制LPS引起的I κ B-α、NF-κ B B p65的磷酸化和TLR 4的表达。以上结果提示，厚朴酚对LPS诱导的急性肺损伤的抗炎作用可能与抑制TLR 4介导的NF-κ B信号通路有关。厚朴酚可能是一种很有前途的治疗急性肺损伤的药物。(C)2012爱思唯尔有限公司版权所有。
Magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis has been reported to have anti-inflammatory properties. The purpose of this study was to evaluate the effect of magnolol on acute lung injury induced by lipopolysaccharide in mice. Male BALB/c mice were pretreated with dexamethasone or magnolol 1 h before intranasal instillation of lipopolysaccharide (LPS). 7 h after LPS administration, the myeloperoxidase in lung tissues, lung wet/dry weight ratio and inflammatory cells in the bronchoalveolar lavage fluid were determined. The levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) in the bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay (ELISA). The extent of phosphorylation of nuclear factor of inhibitory kappa B alpha (I kappa B-alpha), nuclear factor kappa-B (NF-kappa B) p65 and the expression of Toll-like receptor-4 (TLR4) were detected by western blot. The results showed that magnolol markedly attenuated the histological alterations in the lung; reduced the number of total cells, neutrophils, and macrophages in the bronchoalveolar lavage fluid; decreased the wet/dry weight ratio of lungs in the bronchoalveolar lavage fluid; down-regulated the level of pro-inflammatory mediators, including TNF-alpha, IL-1 beta and IL-6; inhibited the phosphorylation of I kappa B-alpha, NF-kappa B p65 and the expression of TLR4, caused by LPS. Taken together, our results suggest that anti-inflammatory effects of magnolol against the LPS-induced acute lung injury may be due to its ability of inhibition TLR4 mediated NF-kappa B signaling pathways. Magnolol may be a promising potential therapeutic reagent for acute lung injury treatment. (C) 2012 Elsevier B.V. All rights reserved.