细颗粒物多组分混合暴露的联合毒性机制研究

Atmospheric fine particles have various particle sizes ranging from nanometer to micrometer and different shapes and compositions, which change with time, temperature, and geographical factors. Furthermore, they adsorb large amounts of inorganic and organic pollutants. Thus it is impossible to study the potential toxicity and toxicity mechanisms by collected atmospheric fine particles. To study the joint toxicity mechanisms of fine particles with multiple components, we plan to use ultrafine carbon particles and silica particles as the basis, on which the heavy metal elements (such as As, Cr, Pb, Cd, and Hg) and organic pollutants (such as benzopyrene (BaP), DDT, and bisphenol A (BPA)) are adsorbed with various amounts. Using this method, more than 50 fine particles are designed and synthesized by high-through synthesis. By studying cell cytotoxicity, ROS generation, and cytotoxic signal pathways, not only can we explore the contribution of various components in fine particles in the cell toxicity, but we can also study the joint toxicity mechanism of fine particles with multiple components. The implementation of this project will be more systematically understanding of the role of different components of fine particles in their toxic effects, thus significantly enhancing the understanding of molecular toxicology and joint toxicity mechanism of fine particles.

大气细颗粒物粒径小，化学组成和结构随时间、温度和地域等因素变化，并且吸附大量无机和有机污染物。多种因素使得以实地采集样品研究大气细颗粒物的毒性及毒性机制难以实现。为研究细颗粒物多种组分混合暴露时的联合毒性机制，本项目拟以超细炭颗粒和氧化硅颗粒为基础，选取重金属元素As、Cr、Pb、Cd、Hg及多环芳烃中的苯并芘（PBA），多氯联苯化合物（DDT）以及双酚A（PaB）为主要研究对象，快速合成50种以上吸附单一或混合重金属和有机污染物的细颗粒物；在对细颗粒物各种组分定量分析基础上，结合实地采集PM2.5颗粒，通过对多种细胞的混合暴露实验探索细颗粒物不同组分在其细胞毒性中的贡献；同时，通过细颗粒物混合暴露对细胞凋亡和ROS等的影响，研究其联合毒性机制。本课题的完成将有助于进一步认识大气细颗粒物不同组分在其环境毒性效应中的作用，从而更准确地理解细颗粒物混合暴露的分子毒理与健康危害机制。

大气细颗粒物粒径小，化学组成和结构随时间、温度和地域等因素变化，并且吸附大量无机和有机污染物。多种因素使得以实地采集样品研究大气细颗粒物的毒性及毒性机制难以实现。为研究细颗粒物多种组分混合暴露时的联合毒性机制，本项目以超细炭颗粒为基础，选取重金属元素As、Cr、Pb、及多环芳烃中的苯并芘（BaP）为主要研究对象，快速合成16种以上吸附单一或混合重金属和有机污染物的细颗粒物；结合实地采集济南地区的PM2.5颗粒，在对细颗粒物各种组分定量分析基础上通过对多种细胞的混合暴露实验探索细颗粒物不同组分在其细胞毒性中的贡献；同时以超细炭颗粒和纳米氧化锌颗粒与Cr(VI)的复合物为基础，通过细颗粒物混合暴露对细胞凋亡和ROS产生等的影响等研究其联合毒性机制。我们发现lnc-PCK1-2:1是一种新型的长链非编码RNA，有着抑制炎症的作用，吸附了Pb的通过抑制新型长链非编码RNA lnc-PCK1-2:1的表达诱导人支气管上皮细胞炎症反应；同时对于同一种重金属离子，不同纳米颗粒可以依据不同机制产生迥异的细胞毒性。本课题的完成将有助于进一步完善我们对细颗粒物不同组分在其环境毒性效应中的作用的认识，从而更准确地理解细颗粒物不同组分的分子毒理与健康危害机制。