PT  - JOURNAL ARTICLE
AU  - Ivetta Dvorakovskaya
AU  - Elena Lebedeva
AU  - Lev Danilov
AU  - Nataliya Kuzubova
TI  - Model of staged development chronic obstructive pulmonary disease (COPD) in rats
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - p3899
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/p3899.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/p3899.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - Models of COPD open ways of studying pathogenesis, searching for therapeutic targets and new health care trends.Aim: To reproduce the successive stages of COPD in experiment.Methods: Model of COPD was induced in Wistar rats by long-time intermittent nitrogen dioxide (NO2) inhalation (15 ppm, 1,5 h/day for 60 days). Histological specimens were stained with hematoxylin-eosin. CD3 expression in bronchial walls and interstitium was determined by immunohistochemistry. TNFα and TGFβ were determined in serum and bronchoalveolar lavage fluid (BALF).Results: After 15-day NO2 exposure acute response to injury was observed: epithelium desquamation and focal proliferation, swelling of submucosa, bronchial gland degeneration, lung tissue hyperextension were revealed. After 30 days cell infiltration of submucosa and hyperplasia of goblet cells were added. After 60-day exposure squamous metaplasia of ciliated epithelium, muscle plate atrophy, focal sclerosis, emphysema were identified. At this stage increase of CD3 expression was revealed in walls of bronchi and interstitium that indicated the presence of large number of T-lymphocytes (61,6±1,59 vs. 28,1±2,36 in control intact rats, p<0,05). TNFα increased in serum (125,9±16,21 vs. 60,9±6,34 pg/ml in control, p<0,05) and BALF (204,9±25,76 vs. 1,5±0,03 pg/ml in control, p<0,05). TGFβ increased in serum 18-fold and in BALF – 8-fold from control (p<0,05).Conclusion: The model allows to reproduce stages of COPD from acute inflammation to lung tissue remoleling (emphysema and focal fibrosis). The model adequacy is confirmed by COPD symptoms: increased expression of CD3-lymphocytes in bronchial walls and lung parenchyma, multiple increased TNFα and growth factor TGFβ.