Role of NLRP3 in the development of silicosis pulmonary fibrosis and the effect of its inhibitor MCC950 / 中国职业医学

ABSTRACT

OBJECTIVE: To investigate the mechanism of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3( NLRP3) inflammasome in the development and progression of silicosis pulmonary fibrosis,and to explore the effect of NLRP3 inhibitor MCC950 on silicosis pulmonary fibrosis. METHODS: The specific pathogen free Wistar male rats were randomly divided into control group,model group and inhibitor group,with 20 rats in each group.The rats in the model group and the inhibitor group were given a 1. 0 m L of free silica suspension at a concentration of 50 g/L by the non-exposure endotracheal intubation method. Rats in the control group were given an equal volume of sterilized 0. 9% sodium chloride solution. Rats in the inhibitor group were given 10 mg/kg body weight of MCC950 once every other day by gavage,while rats in the model group and the control group were given an equal volume of sterilized0. 9% sodium chloride solution. Five rats were randomly sacrificed at 7,14,28,and 56 days after model establishment.The body weight of the rats was weighed,and the degree of pulmonary alveolitis and pulmonary fibrosis was observed. The enzyme-linked immunosorbent assay was used to detect the levels of interleukin( IL)-1β,IL-18 and transforming growth factor-β1( TGF-β1) of lung tissues. Western blotting was used to detect the relative expression of NLRP3 and Caspase-1protein. RESULTS: The body mass of rats increased with increasing observation time( P < 0. 01). The scores of pulmonary fibrosis and the levels of IL-1β,IL-18 and TGF-β1 in lung tissue had statistical significance in the main effect of dust treatment( P < 0. 01),and the order from high to low was model group,inhibitor group and control group( P < 0. 01). At the time points of 7,14,28,and 56 days after model establishment,the score of pulmonary alveolitis and the relative expression of NLRP3 and Caspase-1 protein in lung tissues in the inhibitor group were lower than that of the model group( P < 0. 01),but higher than that of the control group( P < 0. 01). CONCLUSION: The NLRP3/IL-1β/TGF-β1 signaling pathway plays an important role in the development of silicosis pulmonary fibrosis. MCC950 can inhibit the development and progression of pulmonary fibrosis of silicosis by inhibiting the activation of NLRP3 inflammasome.