Silicosis model and drug administration
A single intratracheal exposure to silica suspension was used to establish the silicosis mouse model, simulating the fibrotic state of pneumoconiosis patients (Z. Cao et al., 2020). In brief, after anesthesia with tribromoethanol (i.p., 1.2 mL 100 g-1), mice were given 40 μL of silica suspension at 300 mg mL-1. Sham-operated mice received an equivalent amount of PBS intratracheally. To explore the effect of monotherapy, we divided the mice into six groups at random (9 mice per group): Sham-operated group (abbreviated as PBS), Silicosis control group (abbreviated as Si), Low-dose PFD group (PFD 180 mg kg-1 per mouse, abbreviated as Low PFD), High-dose PFD group (PFD 360 mg kg-1 per mouse, abbreviated as High PFD), Low-dose BIBF group (BIBF 30 mg kg-1 per mouse, abbreviated as Low BIBF) and High-dose BIBF group (BIBF 60 mg kg-1 per mouse, abbreviated as High BIBF). The PBS group and Si group received an equal volume of CMC-Na. Oral gavage was fed once daily for 4 weeks, starting from 6 weeks after silica exposure. To evaluate the effects of combined administration, mice were randomly divided into five groups (9 mice per group): Si group, High PFD group, High BIBF group, Low-dose combined therapy group (PFD 180 mg kg-1 and BIBF 30 mg kg-1 per mouse, abbreviated as Low COM) and High-dose combined therapy group (PFD 360 mg kg-1 and BIBF 60 mg kg-1 per mouse, abbreviated as High COM). The Si group received an equivalent volume of CMC-Na. The administration route, start, and duration of treatment were the same as the previous experiments investigating the efficacy of monotherapy.