A suitable silicosis mouse model was constructed by repeated inhalation of silica dust via nose.

Silicosis as the serious occupational disease is highly necessary to construct a suitable mouse model for disclosing mechanism of occurrence and development in this disease. Here, the volume-effect relationship and volume-based survival curves in mice who inhaled silica suspension intranasally were analyzed. Notable, the optimal volume 80 μl repeated-inhalation by nose to silica suspension in the inbred mouse C57BL/6 J with the highest susceptibility to silicosis led to a great entrance into the lung and a high survival rate after instillation. After repeated-exposure to 20 mg/mL, 80 μl silica for 16 days and then fed without silica exposure until 31 days, weight of mice showed a trend of first decrease and then recover. Moreover, the degree of pulmonary inflammation and fibrosis in mice were analyzed by pathological and immunohistochemistry staining. Transforming growth factor-beta (TGF-β), smooth muscle alpha-actin (α-SMA) and collagen type-I (collagen I, Col-I) were significantly increased in the silica-exposed mouse lung at post-exposure day 16 compared with the controls. Sirius red stain and Micro-CT analysis showed that lung fibrosis formed at post-exposure day 31. This study highlights the critical importance of perfusion volume and repeated nasal drops in inducing inflammatory response and pulmonary fibrosis in silicosis.