Effects of abnormal expression of fusion and fission genes on the morphology and function of lung macrophage mitochondria in SiO2-induced silicosis fibrosis in rats in vivo.

Silicosis is a serious occupational disease affecting millions of related workers. Many studies showed lung macrophages play an important role in the disease. However, the changes of macrophages are not fully characterized and the mechanisms need further investigations. The objectives of this work were to evaluate the effects of abnormal expression of fusion and fission genes on the morphology and function of lung macrophage mitochondria in SiO2-induced silicosis fibrosis in rats. In this study, the rats were injected with 1 mL of SiO2 suspension (100 mg/mL) into the lungs to establish silicosis models, and killed after 30, 60, and 120 days. The rats which were injected with normal saline (1 mL) into lungs were used as control. The lungs of rats were taken for pathological observation. Lung macrophages were collected to measure the number, activity, level of MDA and SOD, and relative content of fusion (Mfn1, Mfn2) and fission (Fis, DRP) genes. Subsequently, mitochondria were extracted from the macrophages to measure the changes of function, including MDA, SOD, ATP, and ATPase. We found that silica dust inhalation led to the proliferation of collagen fibers in the lung tissue. During this process, the number and activity of macrophages increased, the degree of lipid peroxidation increased, and the expression of mitochondrial fusion and fission genes was abnormal. Moreover, the mitochondrial lipid peroxidation level in macrophages increased, the production of ATP and the activity of ATPase decreased, and the abnormal forms of mitochondria occurred. Our results indicated that the morphology and function of mitochondria in macrophages changed during the progress of silicosis, which were related to the abnormal expression of fusion and fission genes.