title: Development of a non-infectious rat model of acute exacerbation of idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease with severe pulmonary fibrosis. The main cause of IPF-associated death is acute exacerbation of IPF (AE-IPF). This study aims to develop a rat model of AE-IPF by two intratracheal perfusions with bleomycin (BLM).
  
  
  METHODS
  Ninety male Sprague Dawley (SD) rats were randomized into three groups: an AE-IPF model group (BLM + BLM group), an IPF model group (BLM group), and a normal control group. Rats in the BLM + BLM group underwent a second perfusion with BLM on day 28 after the first perfusion with BLM. Rats in the other two groups received saline as the second perfusion. Six rats in each group were sacrificed on day 31, day 35, and day 42 after the first perfusion, respectively. Additional 18 rats in each group were observed for survival.
  
  
  RESULTS
  Rats in the BLM + BLM group had significantly worse pulmonary alveolar inflammation and fibrosis than rats in the BLM group. Rats in the BLM + BLM group also developed large amounts of hyaline membrane, showed high levels of albumin (ALB) and various inflammatory factors in the bronchoalveolar lavage fluid (BALF), and had markedly increased lung water content. Furthermore, rat survival was reduced in the BLM + BLM group. The pathophysiological characteristics of rats in the BLM + BLM group resemble those of patients with AE-IPF.
  
  
  CONCLUSIONS
  A second perfusion with BLM appears to induce acute exacerbation of pulmonary fibrosis and may be used to model AE-IPF in rats.
authors.affiliation: Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Soochow University, School of Medicine, Suzhou 215006, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Soochow University, School of Medicine, Suzhou 215006, China.
authors.forename: Zhao-Fang
authors.initials: ZF
authors.lastname: Yin
authors.affiliation: Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai 200433, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai 200433, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai 200433, China.
authors.forename: Ya-Ru
authors.initials: YR
authors.lastname: Wei
authors.affiliation: Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai 200433, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Du
authors.affiliation: Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai 200433, China.
authors.forename: Yue-Ping
authors.initials: YP
authors.lastname: Jin
authors.affiliation: Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai 200433, China.
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai 200433, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai 200433, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Weng
authors.affiliation: Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai 200433, China.
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Li
keywords: Idiopathic pulmonary fibrosis (IPF); acute exacerbation; bleomycin (BLM); model