Establishment and evaluation of chronic obstructive pulmonary disease model by chronic exposure to motor vehicle exhaust combined with lipopolysaccharide instillation
Establishment and evaluation of chronic obstructive pulmonary disease model by chronic exposure to motor vehicle exhaust combined with lipopolysaccharide instillation
复制标题
长期接触机动车尾气联合脂多糖滴注慢性阻塞性肺疾病模型的建立与评价
DOI：
10.1113/ep087077
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发表时间：
2018
影响因子：
2.7
通讯作者：
Wang Jian
中科院分区：
文献类型：
--
作者：
Shu Jiaze;Lu Wenju;Yang Kai;Zheng Qiuyu;Li Defu;Li Yi;Kuang Meidan;Liu Hanwei;Li Ziying;Chen Yuqin;Zhang Chenting;Luo Xiaoyun;Huang Junyi;Wu Xiongting;Tang Haiyang;Wang Jian
新发现本研究的中心问题是什么？在本研究中，我们通过汽车尾气(MVE)联合或不联合注射脂多糖(LPS)的方法，建立、评估和比较了MVE、LPS和MVE+LPS诱导的小鼠慢性阻塞性肺疾病(COPD)模型。主要发现及其重要性是什么？我们的研究表明，长期暴露于MVE并早期注射LPS可以建立具有COPD某些特征的小鼠模型，尽管汽车尾气(MVE)与慢性阻塞性肺疾病(COPD)的发生和加重密切相关，但对MVE与间歇性或慢性亚临床炎症在COPD发病机制中的联合作用知之甚少。因此，鉴于炎症在COPD发生发展中的重要作用，我们希望建立一种既能模拟COPD患者的临床病理变化，又能同时应用MVE暴露和呼吸道炎症的COPD动物模型，对COPD分子机制的研究大有裨益。在本研究中，我们报道了慢性暴露于MVE并气管内滴注脂多糖(LPS)的小鼠成功地建立了COPD，其特征是持续的气流受限、气道炎症、炎性细胞因子产生、肺气肿和小气道重塑。此外，小鼠的心室和血管病理发生了显著变化，包括右室压增加，右室肥厚和肺动脉壁重塑。因此，我们建立了一种新的小鼠COPD模型，将慢性MVE暴露和早期气管内注射内毒素相结合，将使我们能够研究空气污染与COPD发生发展的关系，并探讨其潜在的分子机制。
New FindingsWhat is the central question of this study?In this study, by using motor vehicle exhaust (MVE) exposure with or without lipopolysaccharide (LPS) instillation, we established, evaluated and compared MVE, LPS and MVE+LPS treatment‐induced chronic obstructive pulmonary disease (COPD) models in mice.What is the main finding and its importance?Our study demonstrated that the combination of chronic exposure to MVE with early LPS instillation can establish a mouse model with some features of COPD, which will allow researchers to investigate the underlying molecular mechanisms linking air pollution and COPD pathogenesis.AbstractAlthough it is well established that motor vehicle exhaust (MVE) has a close association with the occurrence and exacerbation of chronic obstructive pulmonary disease (COPD), very little is known about the combined effects of MVE and intermittent or chronic subclinical inflammation on COPD pathogenesis. Therefore, given the crucial role of inflammation in the development of COPD, we wanted to establish an animal model of COPD using both MVE exposure and airway inflammation, which could mimic the clinical pathological changes observed in COPD patients and greatly benefit the study of the molecular mechanisms of COPD. In the present study, we report that mice undergoing chronic exposure to MVE and intratracheal instillation of lipopolysaccharide (LPS) successfully established COPD, as characterized by persistent air flow limitation, airway inflammation, inflammatory cytokine production, emphysema and small airway remodelling. Moreover, the mice showed significant changes in ventricular and vascular pathology, including an increase in right ventricular pressure, right ventricular hypertrophy and remodelling of pulmonary arterial walls. We have thus established a new mouse COPD model by combining chronic MVE exposure with early intratracheal instillation of LPS, which will allow us to study the relationship between air pollution and the development of COPD and to investigate the underlying molecular mechanisms.