Wang Genfa, Mohammadtursun Nabijan, Sun Jing, Lv Yubao, Jin Hualiang, Lin Jinpei, Kong Lingwen, Zhao Zhengxiao, Zhang Hongying, Dong Jingcheng
Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.
The Institutes of Integrative Medicine, Fudan University, Shanghai, China.
Front Physiol. 2018 Feb 6;9:58. doi: 10.3389/fphys.2018.00058. eCollection 2018.
Chronic obstructive pulmonary disease (COPD) is a common cause of mortality worldwide. The current lack of an animal model that can be established within a certain time frame and imitate the unique features of the disease is a major limiting factor in its study. The present study established and evaluated an animal model of COPD that represents the early and advanced stage features using short-, middle-, and long-term sidestream cigarette smoke (CS) exposure. One hundred and nine Sprague-Dawley rats were randomly divided into 10 groups for different periods of sidestream CS exposure or no exposure (i.e., normal groups). The rats were exposed to CS from 3R4F cigarettes in an exposure chamber. Histological analysis was performed to determine pathological changes. We also conducted open-field tests, lung function evaluations, and cytokine analysis of the blood serum, bronchoalveolar lavage fluid, and lung tissue. The lung tissue protein levels, blood gases, and were also analyzed. As the CS exposure time increased, the indicators associated with oxidative stress, inflammatory responses, and airway remodeling were greater in the CS exposure groups than in the normal group. At 24 and 36 weeks, the COPD model rats displayed the middle- and advanced-stage features of COPD, respectively. In the 8-week CS exposure group, after the CS exposure was stopped for 4 weeks, inflammatory responses and oxidative responses were ameliorated and lung function exacerbation was reduced compared with the 12-week CS exposure group. Therefore, we established a more adequate rat model of sidestream CS induced COPD, which will have great significance for a better understanding of the pathogenesis of COPD and drug effectiveness evaluation.
慢性阻塞性肺疾病(COPD)是全球范围内常见的死亡原因。目前缺乏一种能够在特定时间框架内建立并模仿该疾病独特特征的动物模型,这是其研究的一个主要限制因素。本研究通过短期、中期和长期侧流香烟烟雾(CS)暴露,建立并评估了一种代表COPD早期和晚期特征的动物模型。109只Sprague-Dawley大鼠被随机分为10组,分别进行不同时间段的侧流CS暴露或不暴露(即正常组)。大鼠在暴露舱内暴露于3R4F香烟的CS中。进行组织学分析以确定病理变化。我们还进行了旷场试验、肺功能评估以及血清、支气管肺泡灌洗液和肺组织的细胞因子分析。同时分析了肺组织蛋白水平、血气。随着CS暴露时间的增加,与氧化应激、炎症反应和气道重塑相关的指标在CS暴露组中比正常组更高。在24周和36周时,COPD模型大鼠分别表现出COPD的中期和晚期特征。在8周CS暴露组中,停止CS暴露4周后,与12周CS暴露组相比,炎症反应和氧化反应得到改善,肺功能恶化程度降低。因此,我们建立了一种更合适的侧流CS诱导的COPD大鼠模型,这对于更好地理解COPD的发病机制和药物有效性评估具有重要意义。