Abstract：
The widespread occurrence of nanoplastics (NPs), has markedly affected the ecosystem and has become a global threat to animals and human health. There is growing evidence showing that polystyrene nanoparticles (PSNPs) exposure induced enteritis and the intestinal barrier disorder. Lipopolysaccharide (LPS) can trigger the inflammation burden of various tissues. Whether PSNPs deteriorate LPS-induced intestinal damage via ROS drived-NF-κB/NLRP3 pathway is remains unknown. In this study, PSNPs exposure/PSNPs and LPS co-exposure mice model were duplicated by intraperitoneal injection. The results showed that exposure to PSNPs/LPS caused duodenal inflammation and increased permeability. We evaluated the change of duodenum structure, oxidative stress parameters, inflammatory factors, and tight junction protein in the duodenum. We found that PSNPs/LPS could aggravate the production of ROS and oxidative stress in cells, activate NF-κB/NLRP3 pathway, decrease the expression tight junction proteins (ZO-1, Claudin 1, and Occludin) levels, promote inflammatory factors (TNF-α, IL-6, and IFN-γ) expressions. Duodenal oxidative stress and inflammation in PS + LPS group were more serious than those in single exposure group, which could be alleviated by NF-kB inhibitor QNZ. Collectively, the results verified that PSNPs deteriorated LPS-induced inflammation and increasing permeability in mice duodenum via ROS drived-NF-κB/NLRP3 pathway. The current study indicated the relationship and molecular mechanism between PSNPs and intestinal injury, providing novel insights into the adverse effects of PSNPs exposure on mammals and humans.
摘要：
纳米塑料(NPs)的广泛存在，已经明显影响了生态系统，并已成为对动物和人类健康的全球威胁。越来越多的证据表明，聚苯乙烯纳米颗粒（PSNP）暴露会引起肠炎和肠屏障障碍。脂多糖（LPS）可以触发各种组织的炎症负担。PSNPs是否通过ROS驱动的NF-κB/NLRP3途径恶化LPS诱导的肠道损伤仍是未知的。在这项研究中,通过腹膜内注射复制PSNP暴露/PSNP和LPS共暴露小鼠模型。结果表明，暴露于PSNPs/LPS会导致十二指肠炎症和通透性增加。我们评估了十二指肠结构的变化，氧化应激参数，炎症因子，和十二指肠中的紧密连接蛋白。我们发现PSNPs/LPS可以加重细胞内ROS的产生和氧化应激,激活NF-κB/NLRP3通路，降低紧密连接蛋白(ZO-1、Claudin1和Occludin)的表达水平，促进炎症因子(TNF-α，IL-6和IFN-γ)表达。PS+LPS组十二指肠氧化应激和炎症反应较单一染毒组严重,NF-kB抑制剂QNZ可以缓解。总的来说，结果证实PSNPs通过ROS驱动的NF-κB/NLRP3途径恶化了LPS诱导的小鼠十二指肠炎症和通透性增加。目前的研究表明PSNPs与肠道损伤的关系和分子机制。为PSNP暴露对哺乳动物和人类的不利影响提供了新的见解。
