关键词: 矽肺, 转化生长因子-β1, 二氧化硅, 肺纤维化

Abstract: Objective To explore the effects of exposure to different concentrations of SiO₂ on the expression of transforming growth factor-β1（TGF-β1） and the degree of pulmonary fibrosis in silicosis model mice,so as to provide an early warning for exposure to SiO₂ dust in the occupational environment and provide relevant animal data support for the clinical diagnosis and intervention of silicosis. Methods 30 C57BL/6 wild-type male mice aged 10-12 weeks were randomly divided into three groups with 10 mice in each group. The animals were respectively given normal saline,10 mg/mL SiO₂ saline suspension,and 20 mg/mL SiO₂ saline suspension at a dose of 50 μL/mouse by the nasal feeding per day for 28 days,to establish saline control group,low-dose silicosis and high-dose silicosis model groups. After nasal feeding,the body weight of mice was weighed. After 90 days,the lung tissues of mice were taken,and the pathological changes of mice lungs were observed by hematoxylin and eosin（HE） and Masson staining. The paraffin section fluorescence staining and Western blot were used to detect the expression of TGF-β1 in lung tissues. The immunohistochemical staining was used to detect the expression levels of α-SMA,collagen Ⅰ,Fibronectin and N-cadherin. The experimental results were analyzed statistically to determine the relationship between the expression level of cytokine TGF-β1 and the degree of pulmonary fibrosis and SiO₂ exposure. Results During the SiO₂ exposure period,the body weight of mice in the control group was basically normal,and the body weight of mice in the two SiO₂ groups began to decrease significantly on the 20th day. The lung tissue structure at all levels are clear and complete in the control group mice. In the low-dose and high-dose SiO₂ model groups,the lung tissue was found the alveoli collapse,thickening of alveolar interval,increased pulmonary nodules and blue increased collagen deposition. The differences in the pulmonary nodule area and collagen area were statistically significant among three groups（P<0.05）,which were （0.732±0.1447）% and （10.170±1.301）%,（8.126±0.758）% and （11.690±0.9185）%,（31.690±1.897）% and（43.230±2.290）%,respectively. There were statistically significant differences in the expression level of profibrotic proteins,including fibrogenic factor TGF-β1,fibroblast activation markers α-SMA,epithelial-mesenchymal transition key protein N-cadherin,and extracellular matrix collagenⅠ,among the control group,low-dose and high-doseSiO₂ model groups（P<0.05）,and the expression levels were positively correlated with SiO₂ exposure. Conclusion The expression level of pro-fibrotic factor TGF-β1 and the degree of pulmonary fibrosis are positively correlated with the exposure of SiO₂.

Key words: Silicosis, Transforming growth factor, Silica, Pulmonary fibrosis