WANG Chun-Ji, ZHANG Fang, ZHANG Neng-Hua, TANG Jie, XU Long
Nanoplastics/microplastics (NP/MPs), as emerging global contaminants, pose serious threats to ecological systems and human health. Exposure to NP/MPs has been confirmed to be closely associated with gastrointestinal injuries; however, the specific molecular mechanisms underlying NP/MP-induced duodenal damages remain poorly understood. This study aimed to employ an ICR mouse model, using NP/MPs of different sizes (0.08μm, 1μm, and 10μm), to conduct acute (24h) and subacute (28-days) exposure protocols, in order to clarify the primary exposure routes, in vivo distribution characteristics of polystyrene NP/MPs, their effects on duodenal structure and function, and to explore the underlying molecular mechanisms. Acute exposure (250mg/kg, 24h) showed that NP/MPs administered by oral gavage led to the highest accumulation in the abdominal cavity, followed by drinking water and intraperitoneal injection. The accumulated particles were retained and enriched within the small intestinal villi, with a more pronounced enrichment observed for smaller-sized particles. Subacute exposure (50mg/kg for 28d) revealed duodenal structural disruption and reduced goblet cell counts via hematoxylin-eosin (H&E) and alcian blue-periodic acid Schiff (AB-PAS) staining, with no significant particle size-dependent effect observed. Immunofluorescence and Western blotting analyses consistently showed that exposure to NP/MPs of all three sizes significantly reduced the expression of key intestinal tight junction proteins (claudin-1, occludin, and ZO-1) compared to the control group (P < 0.05). Despite this reduction, no particle size-dependent differences in gene expression were observed among the treatment groups. Immunohistochemistry showed upregulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3), interleukin-1β (IL-1β), and interleukin-18 (IL-18) expression. Immunohistochemistry and Western blotting analyses further indicated that the pyroptosis pathway was activated, as evidenced by increased expression of cleaved caspase-1, cleaved caspase-3 (P < 0.001), GSDMD-NT, and GSDME-NT (P < 0.05), suggesting the involvement of the pyroptosis pathway in duodenal injury. This effect did not exhibit a clear size-dependent relationship among the different particle size groups. These results indicate that NP/MPs primarily accumulate in the small intestine via oral exposure, potentially triggering NLRP3-mediated pyroptosis to drive duodenal injuries. Our study provides experimental evidence for understanding the intestinal toxicity mechanisms of NP/MPs and holds scientific significance for assessing their health risks and formulating corresponding protective strategies.
