Abstract
The aim of the present study was to investigate the effect of pirfenidone on bleomycin-induced lung fibrosis in rats, in order to elucidate the underlying mechanism of periostin-induced fibrosis. The lung fibrosis model was constructed using a single intratracheal instillation of bleomycin in rats. The normal rats without bleomycin administration were used as controls (n=24). Bleomycin-treated rats were randomized into the model (M) or pirfenidone (P) group (n=24 per group). Rats were sacrificed on days 7, 14 and 28 following treatment. Hematoxylin-eosin and Masson's trichrome staining were performed to analyze pulmonary alveolitis and fibrosis. Periostin location was detected by immunohistochemistry. Hydroxyproline content, and expression of periostin and transforming growth factor (TGF)-β1 were detected by ELISA, reverse transcription-quantitative polymerase chain reaction or western blotting. Correlation of periostin expression with hydroxyproline and TGF-β1 content was also analyzed. Histological findings demonstrated that pirfenidone significantly inhibited bleomycin-induced lung fibrosis and reduced the hydroxyproline content on day 14 and day 28 compared with the model group (P<0.05 or P<0.01). Furthermore, the bleomycin-induced increased protein expression of periostin and TGF-β1 was also significantly suppressed by pirfenidone on days 14 (P<0.01) and 28 (data not shown). Furthermore, periostin expression was significantly correlated with hydroxyproline and TGF-β1 content, and fibrosis score (P<0.001). The present findings suggest that the antifibrotic effect of pirfenidone may be achieved by suppression of periostin and TGF-β1 expression in rat pulmonary fibrogenesis.