Murine pulmonary fibrosis model induced by repeated low-dose intravenous injection and intratracheal instillation of bleomycin

Abstract

To determine the characteristics and differences in bleomycin-induced lung fibrosis model by repeated low-dose intravenous injection and single dose intratracheal instillation of bleomycin. Forty male ICR (Institute for Cancer Research) mice were randomly divided into a model group I, a model group II, and 2 control groups (10 mice in each group). In model group I, bleomycin was injected intravenously at 10 mg/(kg.d) for 14 consecutive days; and in model group II, bleomycin was instilled intratracheally at 5 mg/kg. The 2 control groups were given isotonic saline solution. At the 28th day, the mice were sacrificed and the bronchoalveolar lavage fluid (BALF) was collected. The total cells and proteins in the BALF, pulmonary coefficient, and hydroxyproline (HYP) content were determined. The pathological changes were observed by the eosin staining and Masson's trichrome staining. 1) Both intravenous injection and intratracheal instillation of bleomycin resulted in severe and extensive inflammation and fibrosis in the lungs. The total cells and proteins in the BALF, HYP content, pulmonary coefficient and the pathological score of pulmonary fibrosis were all significantly increased in the 2 model groups (P<0.01). 2) Fibrosis was mainly under the pleura or around the vessel in model group I, and it was located near the bronehia and bronchioles in model group II. 3) The death rate was higher in the model group II than that in the model group I. 4) Proteins in the BALF were significantly higher in model group II than that in model group I (P<0.05). There was no difference in the total cells in the BALF, the pulmonary coefficient, the HYP content, and the pathological score of pulmonary fibrosis between the 2 groups (P>0.05). The pulmonary fibrosis model can be successfully established by intravenous injection or intratracheal instillation of bleomycin, but the sites of pulmonary fibrosis are different. The histological changes caused by the repeated low-dose intravenous injection of bleomycin is more similar to idiopathic pulmonary fibrosis than that by the single dose intratracheal instillation.