生命早期大气PM1及关键重金属组分暴露对大鼠学习和记忆功能的影响研究

A large number of exogenous magnetic nano-particles from atmospheric particulate matter have been detected in human brain specimens and already attracted broad attention in the world recently, suggesting that fine particles and components in atmospheric particles, especially superfine particulate matter (PM1), can directly enter the brain to harm the central nervous system. Early life (embryos and early childhood) is a critical period of central nervous system growth and development, which are more sensitive to atmospheric particulate matter. However, most of previous researches have studied the overall impact of PM10 or PM2.5 on cognitive function, but very few has paid attention to the effect of exposure in early life to the composition of PM1 on cognitive function, and even fewer has studied the distribution of heavy metals in PM1 in different parts of brain tissue, and the possible association with learning and memory functions. .In this study, experiments of animal inhalation exposure to PM1 will be carried out, based on “an outdoor air PM1 exposure platform” which would be reformed and established according to actual environmental conditions, to study the effect of exposure to PM1 in embryonic and early childhood on cognition such as learning and memory functions, and to explore the relationship between environmental external exposure (the load of heavy metals in PM1)-biological internal exposure (heavy metals in different parts of the brain) - changes in cognitive function (learning and memory functions), searching for the critical heavy metal components that has a greater impact on learning and memory functions.. This study aims to provide scientific data for understanding the toxicity effect of PM1 on central nervous system, and to provide the basic information on health protection for sensitive periods of the relevant population and pollution prevention of atmospheric particulate matter pollution in China.

人脑标本中检测出大量外源性磁铁纳米粒子引起了广泛关注，提示大气颗粒物尤其是超细颗粒物（PM1）可直接进入脑部危害中枢神经系统，特别是生命早期（胚胎和幼儿期）暴露于大气颗粒物其健康影响可能更为严重。以往研究集中于PM10或PM2.5对认知的影响，很少关注PM1及其成分的认知影响，关于PM1及负载重金属在脑组织不同部位的分布和对学习记忆功能改变的研究更少。本研究拟通过改造并建立基于实际环境条件下的“室外大气PM1暴露平台”，开展动物吸入暴露PM1的染毒实验，研究胚胎期和幼儿期PM1暴露对动物学习和记忆等认知功能的影响，探索环境外暴露（PM1上负载的重金属）—生物内暴露（动物脑部不同部位的重金属）—认知功能（学习记忆的改变）间的关系，寻找对学习和记忆影响较大的关键重金属组成。本项目的开展为认识PM1的中枢神经系统毒性效应提供科学数据，为相关人群敏感时期的健康防护和我国大气颗粒物污染防治提供依据。

大气颗粒物污染在全球疾病负担研究中一直位于健康风险因素排名前列，其对人群健康的潜在危害持续获得国内外学者关注，特别是颗粒物对人群中枢神经系统具有潜在影响造成认知功能下降成为研究的焦点。超细颗粒物（PM1）由于其较大的比表面积，更细的粒径，因此造成的潜在危害可能更为严重。但是目前颗粒物与认知功能关系的研究主要集中在较大粒径颗粒物（PM10和PM2.5），关于超细颗粒物（PM1）及负载重金属与学习和记忆功能间关系的研究则很少。为了进一步了解大气PM1及其负载重金属成分污染对生物体学习和记忆功能的影响，本项目详细调研了我国主要城市颗粒物及成分的污染现状；在分析污染现状及前期研究基础上，优化和组装了具有梯度暴露的“室外大气PM1动物暴露平台”，开展了实验动物持续PM1吸入染毒实验；实验动物经过胚胎期和幼儿期暴露后，进一步分析了认知功能的可能改变情况，并获取了实验动物脑组织不同部位进行了内负荷检测。通过研究发现，我国大气颗粒物污染虽然得到一定控制，但污染水平仍然较高，需要关注其对健康的潜在危害；实验动物进行PM1吸入暴露时，暴露期间的PM1浓度及其负载重金属成分的变化与环境监测机构公布的空气质量水平变化趋势较为一致；实验动物经不同梯度PM1吸入暴露后，其脑部不同部位重金属含量有所不同，高PM1暴露剂量组的实验动物脑部海马组织中Al、Fe和Mn元素含量较高，而在额叶皮质中上述3种元素的浓度则较低，不同重金属在不同脑组织中的浓度水平差异可能带来一定的神经系统健康损害；不同梯度PM1吸入暴露后实验动物认知功能行为学测定显示，高PM1暴露剂量组实验动物所需潜伏期时间较长，意味其学习记忆能力的下降；PM1暴露后大鼠的血清甘油三酯（TRIG）和尿素（UREA）随暴露梯度的增加而逐渐升高，揭示PM1持续暴露可改变脂质代谢，同时对心血管系统和肾脏损伤具有潜在风险。