Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Aquat Toxicol. 2023 Sep;262:106659. doi: 10.1016/j.aquatox.2023.106659. Epub 2023 Aug 14.
Microplastics (MPs), a new class of pollutant that threatens aquatic biodiversity, are becoming increasingly prevalent around the world. Fish growth may be severely inhibited by microplastics, resulting in severe mortality. Exposure to microplastics increases the likelihood of intestinal injuries, but the underlying mechanisms remain equivocal. The objective of this study was to investigate the potential toxic mechanisms underlying microplastic-induced intestinal injury in fish and to assist researchers in identifying novel therapeutic targets. In this study, a model of carp exposed to microplastics was established successfully. Histological observation showed that exposure to polyethylene microplastics caused damage to the intestinal mucosal surface and a significant increase in goblet cells, which aggregated on the surface of the mucosa. The mucosal layer was observed to fall off. Lymphocytes in the intestinal wall proliferated and aggregated. TUNEL staining showed that apoptosis occurred in the group exposed to microplastics. The qPCR results showed that the expression of Ferroptosis apoptotic factors COX-2 and ACSL4 was upregulated, while the expression of TFRC, FIH1, SLC7A11, and GPX4 was downregulated. The NF-κB pathway (p-p65, IκBα), inflammatory cytokines (TNF-α, IL-8, IL-6) and apoptosis genes (Bax, Caspase3) were upregulated. Semi-quantitative detection of related proteins by Western blotting was consistent with the gene expression results. In addition, the ELISA assay showed that lipid peroxidation and inflammatory cytokines (TNF-α, IL-1β, IL-6) were increased in the microplastic exposed group. To conclude, lipid peroxidation induced by microplastics activates the NF-κB pathway and causes ferroptosis, ultimately resulting in intestinal damage and cellular apoptosis.
微塑料（MPs）是一种新的污染物，对水生生物多样性构成威胁，在全球范围内日益普遍。微塑料可能严重抑制鱼类生长，导致严重死亡。暴露于微塑料会增加肠道损伤的可能性，但潜在机制仍存在争议。本研究旨在探讨微塑料诱导鱼类肠道损伤的潜在毒性机制，并帮助研究人员确定新的治疗靶点。本研究成功建立了鲤鱼暴露于微塑料的模型。组织学观察表明，暴露于聚乙烯微塑料会导致肠道黏膜表面受损，杯状细胞显著增加，在黏膜表面聚集。黏膜层脱落。肠壁中的淋巴细胞增殖并聚集。TUNEL 染色显示微塑料暴露组发生细胞凋亡。qPCR 结果显示，铁死亡凋亡因子 COX-2 和 ACSL4 的表达上调，而 TFRC、FIH1、SLC7A11 和 GPX4 的表达下调。NF-κB 通路（p-p65、IκBα）、炎症细胞因子（TNF-α、IL-8、IL-6）和凋亡基因（Bax、Caspase3）上调。Western blot 半定量检测相关蛋白与基因表达结果一致。此外，ELISA 检测显示微塑料暴露组的脂质过氧化和炎症细胞因子（TNF-α、IL-1β、IL-6）增加。总之，微塑料引起的脂质过氧化激活了 NF-κB 通路，导致铁死亡，最终导致肠道损伤和细胞凋亡。
