title: Effects and mechanisms of pirfenidone, prednisone and acetylcysteine on pulmonary fibrosis in rat idiopathic pulmonary fibrosis models.
abstract: BACKGROUND
  Previous studies have reported that caveolin-1 (Cav-1) is associated with lung fibrosis. However, the role of Cav-1 expression in pirfenidone-treated idiopathic pulmonary fibrosis (IPF) is unknown.
  
  
  OBJECTIVE
  This study investigated Cav-1 expression in pirfenidone-treated IPF, and compared the effects of pirfenidone with acetylcysteine and prednisone on IPF.
  
  
  METHODS
  Rat IPF model was established by endotracheal injection of 5 mg/kg bleomycin A5 into the specific pathogen-free Wistar male rats. Pirfenidone (P, 100 mg/kg once daily), prednisone (H, 5 mg/kg once daily) and acetylcysteine (N, 4 mg/kg 3 times per day) were used to treat the rat model by intragastric administration for 45 consecutive days, respectively. The normal rats without IPF were used as the controls. After 15, 30 and 45 days of drug treatment, lung histopathology was assessed. The expression of Cav-1 was determined using real-time quantitative PCR and Western blot; the expression of tumour necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) was determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  After 15, 30 and 45 days of drug treatment, comparison of the three drug-treated groups with the model group showed significantly lower (p < 0.05) significance of airsacculitis and fibrosis scores of lung tissues, as well as expression of TGF-β1, TNF-α and PDGF, but the expression of Cav-1 was higher (p < 0.05). Compared with the N group, the fibrosis score was significantly lower and the protein expression of Cav-1 was significantly higher in the P group (p < 0.05). Additionally, the expression of Cav-1 was negatively correlated with the airsacculitis and fibrosis scores (r = -0.506, p < 0.01; r = -0.676, p < 0.01) as well as expression of TGF-β1, TNF-α and PDGF (r = -0.590, p < 0.01; r = -0.530, p < 0.01; r = -0.553, p < 0.01).
  
  
  CONCLUSIONS
  Pirfenidone, prednisone and acetylcysteine can inhibit airsacculitis and pulmonary fibrosis in rat IPF models, which may be related with enhanced caveolin-1, reduced TNF-α, TGF-β1, PDGF.
authors.affiliation: a Department of Respiratory Medicine , The Affiliated Hospital of Qingdao University , Qingdao , China.
authors.forename: Wencheng
authors.initials: W
authors.lastname: Yu
authors.affiliation: b Department of Pediatrics , Laiwu City People's Hospital , Laiwu , China.
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
authors.affiliation: c Department of Intensive Care Unit , The Affiliated Hospital of Qingdao University , Qingdao , China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Song
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001761:Bleomycin; D015153:Blotting, Western; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D054990:Idiopathic Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011241:Prednisone / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C495537:Cav1 protein, rat; D051242:Caveolin 1; D010982:Platelet-Derived Growth Factor; D020011:Protective Agents; D011728:Pyridones; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; C093844:pirfenidone; D011241:Prednisone; D000111:Acetylcysteine
keywords: Caveolin-1; airsacculitis; expression level; platelet derived growth factor; transforming growth factor-β1; tumor necrosis factor-α