SiO₂ particles induce pulmonary fibrosis by modulating NLRP3 through the ROS/Keap1/Nrf2 signaling pathway in rats

Recent studies have shown that the activation of the ROS-dependent NLRP3 inflammasome plays a key role in the pathogenesis of silicosis; however, the mechanism by which SiO₂-induced ROS activates NLRP3 remains unclear. In this study, rats were intratracheally instilled with a SiO₂ suspension once and then received daily intravenous injections of NAC (at doses of 20, 40, and 80 mg/kg, respectively) to inhibit SiO₂-induced ROS. Rats that were intratracheally instilled with a SiO₂ suspension once served as silicosis models, while those that were intratracheally instilled with PBS once served as controls. After 40 days, lung samples were taken for pathological observation, and the BALF was collected to measure ROS levels. The mRNA and protein expression levels of Keap1/Nrf2 signaling indicators (Keap1, Nrf2) and NLRP3 inflammasome indicators (NLRP3, GSDMD) were detected. The results showed that the Keap1/Nrf2 signaling pathway and the NLRP3 were activated in the silicosis rat lungs, accompanied by an increase in ROS levels. When ROS was inhibited, the Keap1/Nrf2 signaling pathway, the NLRP3, and the degree of pulmonary fibrosis were all suppressed in a dose-dependent manner. Therefore, we conclude that SiO₂ particles induce pulmonary fibrosis in rats by modulating the NLRP3 inflammasome via the ROS/Keap1/Nrf2 signaling pathway.