Unilateral Bleomycin-induced Interstitial Pneumonitis Mouse Model With Both a Healthy and a Diseased Lung

A standard mouse model of pulmonary fibrosis has been created by intratracheal or intraperitoneal administration of bleomycin. However, a difficulty presented by this traditional method is its high mortality rate of more than 50% after bleomycin administration. In this study, we aimed to establish a unilateral lung disease model and to assess its feasibility and usefulness.

After 6-week-old C57BL/6 mice were anesthetized, a 1.7Fr microcatheter was advanced into the trachea using an otoscope. Then, 1.0 mg/kg of bleomycin was injected into bilateral lung at the trachea (n=13) or unilateral lung (n=14) after advancing the microcatheter to the left main bronchus under fluoroscopy. Body weight change and survival of bilateral and unilateral lung disease group mice at day 28 were compared using Mann-Whitney and log-rank tests. Lungs were extracted and evaluated using Masson trichrome staining.

Body weights decreased 75.7%±14.0% in the bilateral lung disease group, but were greater, 94.1%±11.4%, in the unilateral lung disease group (p=0.03). Overall survival rates at day 28 were 30.8% and 85.7% in the bilateral and unilateral lung disease groups, respectively. Survival was significantly better in the unilateral lung disease model (p=0.01). Histological evaluation confirmed collagen deposition only in the bleomycin injected lung in the unilateral lung disease model.

Establishing both a healthy and a diseased lung in the same individual model was feasible, achieving lessened body weight loss and more favorable survival. This technique allows for a more efficacious research design, where both the efficacy and adverse effects of a pharmaceutical agent can be evaluated in a single animal.