Subacute dynamic silica dust inhalation induced changes of pathology and cytokines in mouse organs / 中国职业医学

ABSTRACT

OBJECTIVE: To investigate the effects of subacute dynamic silica dust inhalation on the histopathology of major organs and the cytokine changes in lung tissues. METHODS: Male Kunming specific pathogen free mice were randomly divided into control group and dust exposure groups of 3, 14 and 28 d, with 7 mice in each group.The mice of the 3 exposure groups were given for 3, 12 and 24 days with silica dust at a concentration of 1 000.00 mg/m~3 using the self-made automatic dust inhalation device, 6 hours per day and 6 days per week. Rats in the control group were not treated with dust. After the end of treatment, rats were sacrificed. The organ coefficients of the liver, kidney, spleen and lung were calculated. The pathological changes of the organs were observed by hematoxylin-eosin staining method. The pulmonary fibrosis of lung tissues was evaluated by Masson staining method. Sirius scarlet picric acid staining was used to observe the collagen fiber area ratio in lung tissues. Enzyme-linked immunosorbent assay was used to detect the levels of interleukin(IL)-1β, tumor necrosis factor(TNF)-α, transforming growth factor(TGF)-β1 and matrix metalloproteinase 2(MMP-2) in lung tissues. Colorimetric method was used to detect the level of hydroxyproline(HYP) in lung tissues. RESULTS: After the exposure to silica dust, the histology of liver, spleen and kidney tissues were not significantly changed in the mice of the 3 dust exposure groups. The lung organ coefficients increased in the mice of dust exposure groups of 3, 14 and 28 d compared with the control group(P<0.05). The spleen coefficient of mice in dust exposure groups of 3 and 14 d were higher than that in control group(P<0.05). Among the dust exposure groups, the score of pulmonary fibrosis and HYP level in lung tissues were increased with the prolonged dust exposure time(P<0.05). The collagen fiber area ratio of collagenⅠand Ⅲ, and the levels of IL-1β, TGF-β1 and MMP-2 in lung tissues increased in the 3 dust exposure groups compared with the control group(P<0.05). The collagen fiber area ratio of collagen Ⅲ, and the level of IL-1β in lung tissues of the 14 and 28 d of dust exposure group increased(P<0.05), and the TGF-β1 level decreased(P<0.05), when compared with the 3 d group. The collagen fiber area ratio of collagen Ⅰ in lung tissues of 14 d group and the level of MMP-2 in the 28 d group were higher than that of the 3 d group(P<0.05). The level of TNF-α in lung tissues of 14 d group was higher than that of the control group(P<0.05), and while in 28 d group it was lower than those of the other 3 group(P<0.05). CONCLUSION: Subacute dynamic inhalation of silica dust can cause acute lung injury in mice. There is no obvious pathological change in liver, kidney and spleen. The pathological changes of lung tissue are inflammation and fibrosis, and the degree of fibrosis increases with the extension of dust exposure time, and cytokines also changed.