A suitable silicosis mouse model was constructed by repeated inhalation of silica dust via nose. (15th December 2021)

• Record Type: Journal Article
• Authors: Li, Bing; Mu, Min; Sun, Qixian; Cao, Hangbing; Liu, Qiang; Liu, Jiaxin; Zhang, Jinfeng; Xu, Keyi; Hu, Dong; Tao, Xinrong; Wang, Jianhua
• Is Part Of: Toxicology letters. Volume 353(2021)
• Page Start: 1
• Page End: 12
• Publication Date: 2021-12-15
• Subjects: Inhalation exposure -- Instillation by repeated-nasal drop -- Silicosis mouse model -- Chronic silica-induced inflammation -- Lung fibrosis; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2021.09.014
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: A silicosis mouse model was established by repeated inhalation of silica dust via the nose. Silica-induced inflammatory response drives silicon transport. The modified pulmonary fibrosis grading in mice can be provided for judging silicosis progression. μCT image analysis can provide the distribution of silicon nodules in silica-exposed mouse lungs. Abstract: 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.