Abstract: Objective    To investigate the role of Toll-like receptor 4 (TLR4)/nuclear transcription factor κB (NF-κB) pathway in lipid metabolism of alveolar macrophages in the silicosis model of rats induced by silicon dioxide (SiO2).    Methods    According to the random number table method, 36 SD rats were randomly divided into a normal group, a model group and an inhibitor group. The model group and the inhibitor group were modeled by slowly instilling 1 mL of silica suspension into the disposable trachea. After successful modeling, the rats in the inhibitor group were injected with TAK-242 (TLR4/NF-κB signal specific inhibitor) daily with the dose of 0.5 mg/kg. The rats in the normal group and model group were injected an equal dose of normal saline. After 4 weeks, the rats were sacrificed to collect bronchial lavage fluid (BALF). Enzyme-linked immunosorbent assay (ELISA) was used to determine the content of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in BALF of each group of rats. Alveolar macrophages in BALF were extracted and cultured.  Oil red O staining was used to observe the lipid droplet formation of  macrophages in each group. Western blot was used to detect the expression levels of TLR4, MyD88, and NF-κB in macrophages.     Results     Compared with the normal group, the content of IL-6 and TNF-α in the BALF in the model group and the inhibitor group, the proportion of oil red O positive macrophages, the expression of TLR4, MyD88, and NF-κB in phagocytes all significantly increased, and the differences were statistically significant (all P<0.05). Compared with the model group, the content of IL-6 and TNF-α in BALF in the inhibitor group, the proportion of oil red O positive in macrophages, the expression of TLR4, MyD88, NF-κB in macrophages significantly reduced, the differences were statistically significant (all P<0.05). Conclusions     In the silicosis model of rats caused by SiO2, TLR4/NF-κB signal is involved in the regulation of lipid metabolism of alveolar macrophages, and inhibit the expression of TLR4/NF-κB signal, which can significantly inhibit the pathological damage of silicosis.

Key words: Toll like receptor4/ nuclear factor-κB signaling pathway; ,  , Silicosis model induced by silicon dioxide (SiO2); ,  , Alveolar macrophages; ,  , Lipid metabolism