聚苯乙烯纳米塑料通过吸附载脂蛋白E扰乱巨噬细胞胆固醇代谢

Polystyrene nanoplastics disrupt macrophage cholesterol metabolism by adsorbing apolipoprotein E

摘要:

本研究旨在探究污染物纳米塑料(nanoplastics, NPs)对人体健康的潜在危害及其分子机制。聚苯乙烯纳米塑料(polystyrene nanoplastics, PS-NPs)在环境中广泛存在并可进入人体，与心血管疾病风险密切相关，但其对胆固醇代谢的影响尚未明确。本研究通过蛋白质组学技术分析发现，PS-NPs与巨噬细胞相互作用后，可特异性吸附1 676个蛋白质；生物信息学分析表明，这些吸附蛋白显著富集于胆固醇代谢通路，其中对载脂蛋白E (apolipoprotein E, APOE)的吸附最为突出。进一步的分子对接和分子动力学模拟显示，聚苯乙烯分子能够通过竞争性结合APOE的关键氨基酸残基(如LEU-202、TRP-228)，抑制其与胆固醇的相互作用。细胞实验证实，100 μg/mL PS-NPs暴露24 h可显著诱导巨噬细胞内脂质蓄积。本研究从分子互作层面揭示了PS-NPs通过干扰APOE功能影响脂质代谢的新机制，为阐明其促动脉粥样硬化发生的毒理机制提供了关键证据，对评估其健康风险具有重要科学意义。

Abstract:

This study aimed to investigate the potential health hazards and molecular mechanisms of nanoplastic (NP) pollutants. Polystyrene nanoplastics (PS-NPs), which are prevalent in the environment and can enter the human body, have been closely associated with the risk of cardiovascular diseases, yet their impact on cholesterol metabolism remains unclear. In this study, proteomic analysis revealed that PS-NPs specifically adsorbed 1 676 proteins following their interaction with macrophages. Bioinformatic analysis indicated that these adsorbed proteins were significantly enriched in the cholesterol metabolism pathway, with apolipoprotein E (APOE) being the most prominently adsorbed. Further molecular docking and molecular dynamics simulations demonstrated that polystyrene molecules could inhibit the interaction between APOE and cholesterol by competitively binding to key amino acid residues (e.g., LEU-202 and TRP-228) of APOE. Cell experiments confirmed that exposure to 100 μg/mL PS-NPs for 24 h significantly induced lipid accumulation in macrophages. This study reveals, from a molecular interaction perspective, a novel mechanism by which PS-NPs disrupt lipid metabolism by interfering with APOE function. It provides key evidence for elucidating the toxicological mechanism through which PS-NPs promote atherosclerosis and holds significant scientific importance for assessing their health risks.