Development and characterization of a rat model of chronic obstructive pulmonary disease (COPD) induced by sidestream cigarette smoke

Abstract

Cigarette smoke (CS) induced chronic obstructive pulmonary disease (COPD) has been emerging as a great health problem in China. However, lack of appropriate animal model slows down the progress in understanding pathogenesis of the disease. The aim of current study is to establish and evaluate a more adequate rat model of COPD. Study was performed with rats exposed to sidestream cigarette smoke 2h/d and 7d/wk for 2, 4, 6, 8, 10, 12, 24 and 36 wk in a CS chamber (carbon monoxide concentration was 231+/-11ppm). The lung function was determined by using the forced oscillation technique. Pathologic changes were determined by using histological analyses and mucin measurement. Following 36-wk exposure, airway resistance (Raw) and respiratory system elastance (Ers) in CS group rats was elevated by 28.5% and 37.5%, respectively. Up to 4.1-, 2.3- and 1.4-fold increase in the number of neutrophils, macrophages and lymphocytes was observed in the BALF of CS rats. Using quantitative histomorphology techniques, it was found that mean linear intercept (MLI) and mean alveolar airspace (MAA) of CS rats increased by 44.8% and 43.7%, respectively, indicating the occurrence of emphysema. The characteristics of chronic bronchitis including hyperplasia of bronchial epithelial cells, hypersecretion of mucus and development of peribronchial fibrosis were also found in rat lungs. CS group rats showed 43% body weight gain reduction. To conclude, a more adequate sidestream cigarette smoke rat COPD model was established, which will be beneficial for understanding the pathogenesis of the disease and for evaluation of drug effectiveness.