聚苯乙烯纳米塑料在小鼠体内的转运吸收机制和毒性效应评价

环境中纳米塑料的广泛存在严重威胁人类健康，但对其毒性效应尚缺乏深入研究。本项目拟以聚苯乙烯纳米塑料为代表，利用RNA干扰、免疫组化、免疫荧光、透射电镜、电感耦合等离子体质谱等技术，研究纳米塑料在小鼠体内的转运吸收机制和毒性效应。通过纳米塑料暴露小鼠和荧光纳米塑料暴露肠上皮细胞实验，明确纳米塑料在小鼠体内转运吸收与外排的分子机制；基于纳米塑料暴露小鼠实验，检测小鼠长期暴露纳米塑料后肠黏膜组织完整性、氧化应激和免疫功能的变化，研究纳米塑料对小鼠肠黏膜屏障功能的毒性效应；通过金核-聚苯乙烯塑料外壳纳米颗粒暴露小鼠实验，获得小鼠多种组织中纳米塑料浓度，基于毒理毒代动力学/毒效动力学模型，利用三参数Weibull阈值模型预测其风险阈值，进而推算人体健康风险阈值。本项目研究结果不仅能够阐明纳米塑料长期暴露后在小鼠体内的转运吸收机制和毒性效应，还能为探索纳米塑料对人体健康的影响提供实验依据。

The widespread existence of nanoplastics in the environment is a serious threat to human health, and the toxic effect of nanoplastics is still lack of in-depth study. In this project, polystyrene nanoplastics will be used as a representative, and the transportation, absorption and toxic effects of nanoplastics in mice are studied using RNA interference, immunohistochemistry, transmission electron microscopy, immunofluorescence and inductively coupled plasma mass spectrometry (ICP-MS). The absorption, transportation and efflux mechanism of nanoplastics in mice are studied by exposing mice and intestinal epithelial cells with nanoplastics; After long-term exposure of nanoplastics in mice, the changes of intestinal mucosal tissue integrity, oxidative stress and immune function are studied, which can reveal the toxic effects of nanoplastics on intestinal mucosal barrier function; The concentrations of nanoplastics in various tissues of mice are obtained in mice exposed by nanoparticles with Au core and polystyrene plastic shell. Based on the toxicity-based toxicokinetic/toxicodynamic (TBTK/TD) and the three-parameter Weibull model, the risk threshold of nanoplastics is predicted in mice. Furthermore, the risk threshold of nanoplastics in human is evaluated according to risk threshold of mice. The research results of this project will clarify the mechanism of polystyrene nanoplastics transportation and absorption and toxic effects of nanoplastics in mice after long-term exposure, and provide experimental basis for exploring the impact of nanoplastics on human health.