Morphogenesis of lungs in COPD model induced by reactive nitrogen species

Animal models are very important for study of COPD pathogenesis and development of target therapy. Aim: to evaluate the lung morphogenesis during development of nitrogen dioxide-induced COPD model. Methods. Model of COPD was induced in rats by NO 2 (15-19 ppm) inhalation: three 30-min exposures/day with 30 min intervals for 60 days. Lung sections were stained with H&E. Morphometric analysis were performed using the computer program "VideoTest Morpho 3". Results. After 15 days NO 2 acute reaction to injury was observed: submucosal edema, bronchial epithelium desquamation, hyperplasia of lymphoid formations in bronchial walls, edema and infiltration of interalveolar septa, macrophages into alveoli. After 30 days goblet cell hyperplasia, basal membrane denudation, atrophy of muscle plate, signs of hyperextension and lymphocytic infiltration of interalveolar septa were revealed.After 60 days squamous metaplasia, atrophy of bronchial glands, foci of expansion bronchioles and alveolar ducts, signs of emphysema and focal fibrosis were observed. The specific area of interalveolar septa decreased: 14.3±3.1% vs. 26.6±3.1% in intact rats, p<0.05, indicating hyperextension of lung tissue. Deposition of fibrous tissue increased: around lobe bronchus 1.31±0.008 vs.0.97±0.002 mm in intact rats (p<0.05), around lobe artery 1.25±0.005 vs. 1.06±0.002 mm (p<0.05), into interalveolar septa 1.40±0.01 vs. 0.87±0.005 mm (p<0.05). Conclusion. According to histological criteria the lung morphological picture after 60 day exposure to NO2 corresponds to changes in lung manifestations of chronic inflammation, that leads to formation of morphological substrate for the development of irreversible bronchial obstruction.