This study aims to explore the molecular mechanism of tetrandrine (Tet) in alleviating pulmonary inflammation and fibrosis induced by silica (SiO₂) from the perspective of autophagy. C57BL/6J mice were selected as experimental animals, and SiO₂ was exposed by intranasal instillation. Tet was intervened by oral gavage. The mice were euthanized on the 7th and 42nd day of SiO₂ exposure, and lung tissues were collected for histopathological, molecular biological, immunological, and transmission electron microscopy analysis. The results showed that SiO₂ exposure could lead to significant lung inflammation and fibrosis, while Tet could significantly reduce SiO₂ exposure-induced lung inflammation and fibrosis. Molecular mechanism research indicated that, compared with SiO₂ expose group, Tet intervention could significantly reduce the expression levels of inflammatory cytokines and fibrosis markers (TNF-α, IL-1β, MCP-1, TGF-β1, HYP, Col-I, and Fn), and regulate the expression of key molecules ATG7, microtubule-associated protein 1 light chain 3B (LC3B), and P62 in the autophagy pathway to improve the blocking of autophagic flux, promote the recovery of autophagic lysosomal system function, and inhibit apoptosis. In summary, Tet can alleviate silica-induced lung inflammation and fibrosis, which may be achieved by regulating the expression of key molecules in the autophagy process and associated apoptotic pathway.

This study was aimed at investigating the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by smoking—based on bioinformatics analysis and in vitro experimental evidence. The GEO, GEO2R, TargetScan, miRDB, miRWalk, DAVID, and STRING databases were used for bioinformatics analysis. The mRNA expression and the protein levels were determined by real-time PCR and ELISA. After taking the intersection of the diversified results of the databases, four differentially expressed miRNAs (hsa-miR-146a, hsa-miR-708, hsa-miR-150, and hsa-miR-454) were screened out. Subsequently, a total of 57 target genes of the selected miRNAs were obtained. The results of DAVID analysis showed that the selected miRNAs participated in COPD pathogenesis through long-term potentiation, the TGF-β signaling pathway, the PI3K-Akt signaling pathway, etc. The results of STRING prediction showed that TP53, EP300, and MAPK1 were the key nodes of the PPI network. The results of the confirmatory experiment showed that, compared with the control group, the mRNA expression of ZEB1, MAPK1, EP300, and SP1 were up-regulated, while the expression of MYB was down-regulated and the protein levels of ZEB1, MAPK1, and EP300 were increased. Taken together, miRNAs (hsa-miR-146a, hsa-miR-708, hsa-miR-150, and hsa-miR-454) and their regulated target genes and downstream protein molecules (ZEB1, EP300, and MAPK1) may be closely related to the pathological process of COPD.

The long-term inhalation of free silica dust causes silicosis—a prevalent occupational hazard—yet its systemic effect on male reproductive toxicity remains underexplored. Tetrandrine (Tet) is the only plant-derived anti-silicosis drug approved in China. This study investigates silica (SiO₂) -induced male reproductive damage and evaluates Tet’s protective effects. Sixty male C57BL/6 mice (6–8 weeks) were divided into control, SiO₂ exposure, and SiO₂ + Tet groups. SiO₂ was administered via intranasal infusion and Tet via gavage. Mice were sacrificed at day 7 (male reproductive injury model corresponding to the pulmonary inflammation stage) and day 42 (male reproductive injury model corresponding to the pulmonary fibrosis stage). Analyses included sperm morphology, testicular transcriptome sequencing, RT-qPCR, and immunofluorescence. At day 7, SiO₂ exposure upregulated testicular inflammatory markers, which were partially mitigated by Tet. At day 42, SiO₂ increased sperm deformity and testicular fibrosis markers (fibronectin and vimentin); Tet intervention reduced these abnormalities. Transcriptome analysis revealed distinct gene expression patterns at day 7 versus day 42, indicating time-dependent injury mechanisms. Tetrandrine alleviates silica-induced reproductive damage in male mice, suggesting potential therapeutic applications for occupational silica exposure and expanding the understanding of silica toxicity beyond the respiratory system.