城市道路空气超细颗粒物对中枢神经系统毒性及其作用机制研究

Ultrafine particles (UFPs, <0.1 μm) in the atmospheric particulates are composed of transition metals, organic matters, endotoxins, etc. They are small in grain size, light in mass, but occupy large proportion in quantity of particulate matters (PM). The effects of UFPs on health of exposed population arose more and more attention in recent years. Previous researches about this issue were mainly focused on UFPs' effects on respiratory system and cardiovascular system. Whether and how can they influence central nervous system (CNS) is still indefinite. Several reports indicated that UFPs can enter the CNS through different ways, so probably they may induce some negative influences to CNS of the outdoor workers, who are exposed to UFPs chronically. Actually UFPs are nano-sized particles, but studies about such mixed nano materials are still deficient though many researches about single nano materials have achieved some results. We plan to investigate the effects of UFPs on CNS by experimentation on animals and cultured brain cells. Furthermore, we want to explore possible mechanisms of their effects, such as oxidative stress, inflammatory reaction, mitochondrial damage and apoptosis. This study may provide experimental data and theoretical reference for researches about effect of urban air pollution on CNS of exposed population.

大气颗粒物中的超细颗粒物（<0.1 μm，UFPs）是由过渡金属、有机物、内毒素等组成的混合物，具有粒径小、质量轻、数量多等特点，最易进入人体，其与人群健康的关系近年来愈加引起关注。以往研究主要集中于其对呼吸系统及心血管系统的影响，而其对中枢神经系统（CNS）的影响尚缺乏确切认识；有研究提示UFPs可通过不同途径进入CNS，而某些城市道路相关作业者长期暴露于大量UFPs中，可能对这类职业人群CNS造成潜在危害。UFPs粒径已达纳米级，而目前仅在单一纳米物质的CNS毒性研究中取得一些初步成果，缺乏对此类混合纳米颗粒物的毒性研究。本研究拟利用动物实验及体外培养细胞实验对UFPs的CNS毒性作用进行系统研究，并从氧化应激、炎性反应、线粒体损伤、凋亡水平变化这几个层次选取相关的观察指标和靶点，对UFPs影响CNS的机制进行探讨，为城市空气污染对相关暴露人群CNS影响的研究提供实验依据及理论参考。

本研究利用专业大气颗粒物采样装置采集城市道路空气中的超细颗粒物进行动物在体及体外试验，观察其对中枢神经系统可能的毒性作用，并对其作用机制进行初步探讨。研究发现将颗粒物经气管滴注染毒可引起大鼠CNS出现一系列功能性及病理性改变，颗粒物加入培养液染毒也可引起体外培养神经细胞出现明显的毒性效应，对其毒作用机制进行探索，认为超细颗粒物造成中枢神经系统损伤的毒理学机制可能与一系列细胞事件有关，即UFPs可引起细胞内氧化应激反应增强，过多的自由基对线粒体等膜性结构产生影响，使线粒体功能出现障碍，进而引起细胞内多种信号级联反应，启动凋亡通路，出现细胞凋亡率升高，最终导致组织坏死等更为严重的病理改变。本研究提示，城市道路空气中存在的超细颗粒物经呼吸道吸收进入体内后，可能对交警、道路清洁工等职业人群及其他密切接触人群的中枢神经系统造成潜在危害，对这类人群的健康防护尤其是呼吸道防护应受到充分重视。