Establishment and Evaluation of a Rat Model of Sidestream Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease.

Genfa Wang,Nabijan Mohammadtursun,Zhengxiao Zhao,Jing Sun,Hongying Zhang,Jinpei Lin,Jingcheng Dong,Lingwen Kong,Hualiang Jin,Yubao Lv

doi:10.3389/fphys.2018.00058

Abstract

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.

Highlights

Chronic obstructive pulmonary disease (COPD), a complex inflammatory disease, involves the destruction of the lung parenchyma and chronic inflammation of the peripheral airways, which leads to progressive airway narrowing and dyspnea (Lamprecht et al, 2011; Song et al, 2016)
The data are expressed as the mean ± standard deviation. *p < 0.05 and **p < 0.01 indicate a statistically significant difference compared to the normal group. #p < 0.05 and ##p < 0.01 indicate a statistically significant difference between the M5 group and the M4 group
It was reported that a rat model is a poor animal model because rats are relatively resistant to COPD model establishment (Groneberg and Chung, 2004; Stevenson et al, 2007)

Summary

Introduction

Chronic obstructive pulmonary disease (COPD), a complex inflammatory disease, involves the destruction of the lung parenchyma and chronic inflammation of the peripheral airways, which leads to progressive airway narrowing and dyspnea (Lamprecht et al, 2011; Song et al, 2016). COPD has posed a substantial health care burden on many countries for centuries. It is the third leading cause of global death, based on the most recent figures from the Global Burden of Disease Study (Lozano et al, 2012; McLean et al, 2016). New therapeutic approaches have emerged but cannot fully counteract the progressive decline in lung function, which leads to disability and death, because the mechanisms underlying COPD are not well understood. Animal models have been a key factor in forming objective views regarding the pathogenesis of COPD. An animal model offers the best approach for studying all chronic diseases, such as COPD (Canning and Wright, 2008)

Objectives

Methods

Results

Conclusion