微塑料对生长期雄性小鼠脂质代谢干扰及机制研究

Microplastics (MPs) could be ingested by humans and other terrestrial mammals via food and other pathways. MPs are hard to be digested and utilized by animals. Therefore, normal lipid metabolism in animals could be potentially disturbed by MPs. In addition, oxidative stress induced by MPs is also one of the potential reasons of abnormal lipid metabolism in vivo. Many diseases in the body are closely related to lipid metabolism disorders. Children and adolescents in growing periods are highly sensitive to environmental pollutants, and lipid metabolism plays an important role in their growth and development. However, there is no in-depth study on the interference of MPs on lipid metabolism in children and adolescents at the level of lipid molecules. To address this scientific question, the polystyrene spherical MPs and 3-week old C57/B6 male mice will be selected as model pollutants and animals, respectively. Based on modern high resolution nuclear magnetic resonance spectroscopy (NMR), the interference of MPs on lipid molecules in different tissues of growing mice was explored by using non-targeting lipidomics. Finally, the mechanisms of lipid metabolism in growing mice induced by MPs will be elaborated from the perspective of lipidomics, and the biomarkers for early-stage exposure to MPs will be identified and characterized. The findings will facilitate decision-making for the authorities to control increasing MPs in the future.

微塑料能够通过摄食途径进入人类和其他陆生哺乳动物体内。微塑料在体内难以被消化利用，具有潜在干扰体内脂质代谢的危害。此外，微塑料导致的氧化应激也是体内脂质代谢异常的潜在原因之一。体内众多疾病与脂代谢紊乱密切相关。处于生长期内的儿童和青少年对环境污染物具有高度敏感性，且脂代谢在其成长发育期间起到重要作用。但目前还未有从脂质分子水平深入探究微塑料对儿童和青少年体内脂质代谢干扰的相关研究。针对上述研究需求，本项目选取聚乙烯微塑料作为目标污染物，3周龄C57/B6雄性小鼠为模式动物进行暴露实验。基于现代高分辨率核磁共振波谱技术（NMR），从非靶向脂组学角度重点探究微塑料对生长期小鼠不同组织脂质分子干扰规律。最终从脂组学角度阐述微塑料对生长期小鼠体内脂质代谢干扰的潜在机制，并筛选可供预警使用的生物标志物。研究结果可为未来管控环境中日益增多的微塑料提供决策依据。

目前已证实微塑料能够通过饮食、呼吸等途径被人类和其他陆生哺乳动物摄入体内，继而导致健康风险。处于生长期内儿童和青少年对有害污染物具有高度敏感性，因此可能更易受到微塑料的侵害。但迄今为止还鲜有针对生长期内人群或模式动物暴露微塑料的健康风险研究。本项目较为系统考察了微塑料于生长期小鼠体内的富集分布规律；微塑料对生长期小鼠体内氧化应激水平及等生理、病理的影响规律；在此基础上整合、优化脂质组学和转录组学等分析平台，深入考察分析微塑料对生长期小鼠体内脂质干扰以及潜在机理。项目严格按照预期的研究目标及内容展开。研究结果揭示了微塑料于生长期小鼠肝脏及肠道中富集分布存在明显的粒径及剂量效应。微塑料可以导致生长期小鼠体内氧化应激水平上升、脂质代谢紊乱、病理损伤等毒性效应且与微塑料的粒径及浓度存在明显关联。多组学研究进一步揭示脂肪酸、脂质合成及代谢通路异常是导致脂质代谢紊乱的潜在机理。筛选出的差异变化的脂质可作为评估微塑料生物毒性标志物。本项目的研究结果进一步丰富了微塑料于体内的毒性数据，可为未来微塑料危害评估及管控提供理论依据及技术支撑。