Inhalation of glycopyrronium inhibits cigarette smoke-induced acute lung inflammation in a murine model of COPD
Inhalation of glycopyrronium inhibits cigarette smoke-induced acute lung inflammation in a murine model of COPD
复制标题
吸入格隆铵可抑制慢性阻塞性肺病小鼠模型中香烟烟雾引起的急性肺部炎症
DOI：
10.1016/j.intimp.2013.12.021
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发表时间：
2014-02-01
影响因子：
5.6
通讯作者：
Xie, Qiang-min
中科院分区：
文献类型：
--
作者：
Shen, Liang-liang;Liu, Ya-nan;Xie, Qiang-min
格隆溴铵（GB）是一种毒蕈碱受体拮抗剂，已被用作慢性阻塞性肺疾病（COPD）患者的长效支气管扩张剂。本研究的目的是研究吸入GB在香烟烟雾诱导的急性肺部炎症小鼠模型中的抗炎活性。我们发现，烟雾预处理与GB抑制中性粒细胞和巨噬细胞在支气管肺泡灌洗液（BALF）在香烟烟雾（CS）暴露小鼠的积累。GB在300和600 μ g/ml剂量下显著抑制CS诱导的肺组织和BALF中白细胞介素（IL）-1 β肿瘤坏死因子（TNF）-α、单核细胞趋化蛋白（MCP）-1和转化生长因子（TGF）-β 1的mRNA和蛋白表达水平的增加。此外，GB在600 μ g/ml的剂量显著抑制谷胱甘肽（GSH）和髓过氧化物酶（MPO）活性的变化，降低CS诱导的基质金属蛋白酶（MMP）-9的表达，并通过肺组织的免疫组织化学染色确定增加CS诱导的金属蛋白酶组织抑制剂（TIMP）-1的表达。我们的研究结果表明吸入GB对COPD炎症反应的有益作用。(C)2013年由Elsevier B. V.出版
Glycopyrronium bromide (GB) is a muscarinic receptor antagonist that has been used as a long-acting bronchodilator in chronic obstructive pulmonary disease (COPD) patients. The aim of this study was to investigate the anti-inflammatory activity of inhaled GB in a cigarette smoke-induced acute lung inflammation mouse model. We found that aerosol pre-treatment with GB suppresses the accumulation of neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) in cigarette smoke (CS)-exposed mice. GB at doses of 300 and 600 mu g/ml significantly inhibited the CS-induced increases in the mRNA and protein expression levels of interleukin (IL)-1 beta tumor necrosis factor (TNF)-alpha, monocyte chemotactic protein (MCP)-1 and transforming growth factor (TGF)-beta 1 in lung tissues and the BALF. Moreover, GB at a dose of 600 mu g/ml significantly inhibited the CS-induced changes in glutathione (GSH) and myeloperoxidase (MPO) activities in the BALF, decreased the CS-induced expression of matrix metalloproteinases (MMP)-9, and increased the CS-induced expression of tissue inhibitor of metalloproteinases (TIMP)-1, as determined through the immunohistochemical staining of lung tissue. Our results demonstrate the beneficial effects of inhaled GB on the inflammatory reaction in COPD. (C) 2013 Published by Elsevier B.V.