机动车来源的大气超细颗粒物诱发自噬相关生物效应机制研究

Haze poses serious risks to public health and has aroused highlighted public concerns in China. It has been proposed that fine particles have the greatest potential for toxicity. Motor vehicle exhaust is a main long-term source of urban atmospheric fine particles and more than 90% of the particles are ultrafine particles (nanoparticles). In contrast, the exact toxicological mechanism of atmospheric ultrafine particles from motor vehicle exhaust still remains to be further investigated in China. Autophagy is a catabolic process responsible for cellular homeostasis and stress response, with an astonishing number of connections to human disease and physiology. It has been considered a common biological response of nanoparticles and emerging mechanism of nanotoxicity. This project aims to explore the critical scientific issue of autophagy-related biological effects and underlying mechanism of atmospheric ultrafine particles from motor vehicle exhaust; to characterize the ultrafine particles derived from gasoline, diesel and natural gas exhaust in China; and to clarify how diverse ultrafine particles induce cytotoxicity, immune response and pathological process by disturbing autophagic flux on respiratory systems at the cellular and animal level. We will elucidate the relationship between properties and the biological effects of different particles, and at the same time, provide the fundamental evidence for revealing the health hazards of atmospheric fine particles and haze prevention.

霾污染已成为影响我国居民健康的重大社会问题，其危害主要来自其中的细颗粒物。机动车排放是我国城市大气细颗粒物的长期与主要来源，其中90%为超细（纳米）颗粒物；而目前国内该来源大气超细颗粒物的确切毒理机制仍有待深入研究。自噬是细胞维持内稳态和抵御环境压力的应激调控机制，具有重要的病生理意义，也是纳米材料介导生物与毒性效应的主要机制。本项目拟针对大气超细颗粒物的自噬相关生物毒性效应机制这一关键科学问题，以国内现有汽油、柴油和天然气机动车来源的大气超细颗粒物为研究重点，利用大气颗粒物呼吸暴露相关的细胞和动物病生理模型，探索不同来源颗粒物影响细胞完整自噬流、介导生物损伤的分子机制，深入研究颗粒物经自噬诱导免疫信号胞外传递、引发机体免疫及病理反应的机制，系统分析颗粒物性质与其自噬相关生物效应间的关系；以期为深入了解我国霾污染引发健康效应的内在毒理机制、促进城市大气污染的有效人群疾病防治提供科学依据。

随着人们对霾污染的认识不断深入，大气细颗粒物的毒理机制与健康危害成为环境领域的重大科学问题。机动车来源的细/超细颗粒物是城市大气细颗粒物的重要成分和长期来源，可能通过细胞自噬这一重要的应激调控机制介导生物及毒性效应。本项目以国内主要类型汽油和柴油机动车以及北京市实际交通道路来源的大气细/超细颗粒物为研究重点，分析不同来源颗粒物的重要理化特征及其引发的自噬相关生物效应，探索了microRNAs调控自噬的相关分子毒性机制，揭示了大气颗粒物与大气有害气体成分协同诱导细胞内质网应激的毒性作用通路及效应分子；同时设计制备多种荧光纳米模式颗粒物，为大气超细颗粒物的细胞内分布、示踪与表征进行了前期探索，并研究了模式颗粒物的细胞摄取、转运及清除等重要过程及其膜泡相关机制。本项目研究结果将为深入了解我国大气细颗粒物引发健康效应的毒理机制、促进城市霾污染相关疾病防治提供科学依据。