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Comparison of in vivo anti-fibrotic effects of pirfenidone and nintedanib in bleomycin-induced pulmonary fibrosis model
Authors:Lü Zi-wei  HUANG Kai  GAN Wen-hua  GAO Shao-yan  YANG Bo  HELIAN Kai-yue  LI Xiao-he  ZHOU Hong-gang
Abstract:AIM: To compare the effects of pirfenidone and nintedanib on bleomycin-induced mice pulmonary fibrosis model in different periods. METHODS: Five mice models were established according to the schedule of drug administration:a inflammatory phase model and 4 fibrotic phase models including the early prevention study group, early therapy study group, late therapy study group and full-course therapy study group. The indicators of lung inflammatory and lung fibrosis were detected respectively. RESULTS: (1) The level of anti-inflammatory and antioxidant indicators:both pirfenidone and nintedanib reduced the number of inflammatory cells and inhibited the secretion of inflammatory factors. Pirfenidone had a better effect on inhibition of interleukin (IL)-1β and IL-4 (P < 0.01), while nintedanib had a better effect on inhibition of IL-6 and IFN-γ (P < 0.05). Pirfenidone significantly increased superoxide dismutase (SOD) activity (P < 0.01), and nintedanib significantly reduced malondialdehyde (MDA) and myeloperoxidase (MPO) levels (P < 0.01). (2) Collagen content in lung tissue:the inhibitory effect of nintedanib on hydroxyproline content in mouse lung was better than that of pirfenidone in the early therapy study group, late therapy study group and full-course therapy study group of the fibrotic phase models (P < 0.05). Pirfenidone had a better inhibitory effect on hydroxyproline content than nintedanib in the early prevention study group (P < 0.01). (3) Pathological evaluation of lung tissue:both pirfenidone and nintedanib reduced the inflammatory infiltration and fibrotic area of the lung tissues. The inhibition trend was consistent with that of collagen content. CONCLUSION: Both pirfenidone and nintedanib have anti-inflammatory, anti-oxidative and anti-fibrosis effects in bleomycin-induced pulmonary fibrosis in mice. Pirfenidone is more effective in the early prevention study group, and nintedanib has a better effect in early therapy study group, late therapy study group and full-course therapy study group.
Keywords:Idiopathic pulmonary fibrosis  Pirfenidone  Nintedanib  Inflammation  Oxidative stress  
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