Effect and mechanism of etanercept on pulmonary fibrosis in mice induced by bleomycin / 中国免疫学杂志

ABSTRACT

Objective:To observe the effect of etanercept on bleomycin-induced pulmonary fibrosis in mice and its possible mechanisms.Methods:Thirty male SPF Kun ming mice were randomly assigned to control group ( intratracheal saline injection ) or model group ( intratracheal injection of bleomycin 5 mg/kg ) or intervention group ( intratracheal bleomycin injection followed by etanercept 3 mg/kg intraperitoneal administration twice a week )(n=10 group).Lung tissue were taken after the sacrifice of the mice with 28 days of molding.The content of hydroxyproline of the right lung samples was measured by alkaline hydrolysis method ,while the left lungs were fixed in 4%paraformaldehyde and embedded in paraffin with the sections stained with hematoxylin -eosin or Masson′s trichrome for pathological examination .Total tissue protein was extracted from lung homogenates to detect the expression of NF -κB and phosphorylation of NF-κB( P-NF-κB) by Western blot.Results:The content of hydroxyproline in lung tissue of mice of intervention arm was decreased significantly compared with the model arm ( P<0.01 ).The alveolar structure of the intervention arm maintained integrity with alveolar septum slightly thickened.The inflammation and fibrosis scores were decreased significantly with noticeable greater improvement of pulmonary fibrosis than the model arm (P<0.01).In addition,the protein phosphorylation of NF-κB in the lung tissues was remarkably decreased in the intervention arm ( P<0.01 ).Conclusion: Etanercept can inhibit the phosphorylation of NF-κB and reduce lung inflammation and fibrosis caused by bleomycin in mice ,which may be useful in the treatment of pulmonary fibrosis.