Effects of bosentan on pulmonary fibrosis

Abstract

Objective To investigate the effects of bosentan on pulmonary fibrosis.Methods Forty-eight male Wistar rats were randomly and equally divided into control groups (C2,C4),model groups (F2,F4) and drug groups (D1,D2).Bleomycin was used to create pulmonary fibrosis model,while rats in D1 and D2 groups were treated by bosentan from day 2 and day 15.Plasma endothelin-I (ET-1),matrix metalloproteinase-9 (MMP-9) and tissue inhibitorof metalloproteinase (TIMP)-1 were measured.Alveolitis and fibrosis scores were assessed after 2 and 4 weeks.Results (1) The levels of ET-1 in F4 group were highest,followed by F2,C4 and C2 groups [(0.41 ±0.13),(0.28 ±0.08),(0.11 ±0.04),and (0.10 ±0.05) μg/L].Compared to F4 group,the levels of ET-1 in D1 group was reduced,but no significant difference was found between D2 and F4 groups; (2) Pathological assessment showed that alveolar structure was destroyed,and numerous inflammatory cells and fibroblasts could be seen in F2 group as well as collagen,most significantly in F4 group,and those were significantly reduced in D1 group as compared with F4 ; (3) The levels of ET-1 were positively associated with alveolitis and fibrosis scores,but MMP-9/TIMP-1 were negatively with them.Conclusion Bosentan can protect against the bleomycin-induced pulmonary fibrosis,and the improvement is more significant in early stage. Key words: Bosentan; Bleomycin ; Pulmonary fibrosis ; Endothelin-1