超细颗粒物（ultrafine particles, UFPs），即空气动力学直径小于100纳米的颗粒物，是大气颗粒物的关键毒性组分。虽然其质量微乎其微，但对大气颗粒物的数量贡献极高。大气中的超细颗粒物可被人体吸入肺部，进入循环系统，并扩散到全身多个组织和器官，对人体健康产生直接的损伤。因此，超细颗粒物暴露的健康效应研究关注度越来越高，但目前为止健康效应的证据及内在的生物学机制尚不明确。
2016年至2017年，朱彤教授课题组与北京大学第一医院及北京市西城区什刹海社区卫生服务中心开展合作，于什刹海周边社区招募了135名受试者，并完成了410次重复随访的定群研究。研究团队于什刹海社区卫生服务中心楼顶搭建大气污染监测站，对健康随访前两周的大气细颗粒物、超细颗粒物、碳质组分等污染物进行连续监测。研究发现，健康随访前平均1至13天超细颗粒物暴露与受试者空腹血糖水平的升高显著相关，且随着累积暴露时间窗口的增加，空腹血糖水平升高的幅度也在逐渐增加（图1）。敏感性分析和双污染物模型结果表明超细颗粒物UFPs暴露与空腹血糖水平之间的关联非常稳健和显著。
图1. 随访前平均1至13天大气污染物暴露与受试者空腹血糖水平之间的关联，其中超细颗粒物UFPs有显著关联。
为了探究超细颗粒物暴露与空腹血糖升高关联的潜在机制，研究团队对受试者全血样本进行了RNA提取和转录组高通量测序，通过耦合线性混合效应模型的中介效应模型寻找与超细颗粒物暴露和空腹血糖水平升高显著相关的转录本（图2）。进一步使用MetaCoreTM数据库进行富集分析，发现这些转录本与前体激素阿黑皮素原经分解生成多种激素、缺氧诱导因子-1功能的调控、泛醌的代谢、抗原呈递中主要组织相容性复合体的作用等通路显著相关（图3）。
图2. 与超细颗粒物暴露和空腹血糖水平升高显著相关的转录本
该研究增加了超细颗粒物短期暴露导致健康损伤的流行病学证据，并为探索污染物暴露后健康指标水平变化的潜在机制提供了新的见解，提示未来研究应更多地关注大气中超细颗粒物暴露对人体健康的影响和机制。
图3. 与超细颗粒物暴露和空腹血糖水平升高显著相关的转录层面通路
相关研究成果以“Transcriptional pathways of elevated fasting blood glucose associated with short-term exposure to ultrafine particles: A panel study in Beijing, China”为题，发表于Journal of Hazardous Materials上。北京大学环境科学与工程学院博士生姚媛和陈曦博士为该论文共同第一作者，朱彤教授为通讯作者。该项研究获得科技部973项目（2015CB553401）、国家自然基金委重大项目（21190051）、创新群体项目（41421064、41121004）等的支持。
团队已发表的相关文章：
- Yao Y, Chen X, Chen W, Gao K, Zhang HXY, Zhang LN, Han YQ, Xue T, Wang Q, Wang T, Xu YF, Wang JX, Qiu XH, Que CL, Zheng M, Zhu T. Transcriptional pathways of elevated fasting blood glucose associated with short-term exposure to ultrafine particles: A panel study in Beijing, China. Journal of Hazardous Materials, 2022, 430, 128486. https://doi.org/10.1016/j.jhazmat.2022.128486
- Chen X, Luan MX, Liu JM, Yao Y, Li XY, Wang T, Zhang HXY, Han YQ, Lu XC, Chen W, Hu XY, Zheng M, Qiu XH, Zhu T. Risk factors in air pollution exposome contributing to higher levels of TNFα in COPD patients. Environment International, 2022, 159, 107034. https://doi.org/10.1016/j.envint.2021.107034
- Gao K, Chen X, Zhang LN, Yao Y, Chen W, Zhang HXY, Han YQ, Xue T, Wang JX, Lu LP, Zheng M, Qiu XH, Zhu T. Associations between differences in anemia-related blood cell parameters and short-term exposure to ambient particle pollutants in middle-aged and elderly residents in Beijing, China. Science of the Total Environment, 2022, 816, 151520. https://doi.org/10.1016/j.scitotenv.2021.151520
- Yao Y, Chen X, Chen W, Han YQ, Xue T, Wang JX, Qiu XH, Que CL, Zheng M, Zhu T. Differences in transcriptome response to air pollution exposure between adult residents with and without chronic obstructive pulmonary disease in Beijing: A panel study. Journal of Hazardous Materials, 2021, 616, 125790. https://doi.org/10.1016/j.jhazmat.2021.125790
- Yao Y, Chen X, Chen W, Wang Q, Fan YF, Han YQ, Wang T, Wang JX, Qiu XH, Zheng M, Que CL, Zhu T. Susceptibility of individuals with chronic obstructive pulmonary disease to respiratory inflammation associated with short-term exposure to ambient air pollution: A panel study in Beijing. Science of the Total Environment, 2021, 766, 142639. https://doi.org/10.1016/j.scitotenv.2020.142639
- Chen X, Que CL, Yao Y, Han YQ, Zhang HXY, Li XY, Lu XC, Chen W, Hu XY, Wu YS, Wang T, Zhang LN, Zheng M, Qiu XH, Zhu T. Susceptibility of individuals with lung dysfunction to systemic inflammation associated with ambient fine particle exposure: A panel study in Beijing. Science of the Total Environment, 2021, 788, 147760. https://doi.org/10.1016/j.scitotenv.2021.147760
- Gao K, Chen X, Li XY, Zhang HXY, Luan MX, Yao Y, Xu YF, Wang T, Han YQ, Xue T, Wang JX, Zheng M, Qiu XH, Zhu T. Susceptibility of chronic obstructive pulmonary disease patients to cardiovascular autonomic dysfunction in association with short-term exposure to metals in ambient fine particles: A panel study in Beijing, China. Science China: Life Sciences, 2021, 64. https://doi.org/10.1007/s11427-020-1912-4
- Liu JM, Chen X, Qiu XH, Zhang HXY, Lu XC, Li HN, Chen W, Zhang LN, Que CL, Zhu T. Association between exposure to polycyclic aromatic hydrocarbons and lipid peroxidation in patients with chronic obstructive pulmonary disease. Science of the Total Environment, 2021, 780, 146660.https://doi.org/10.1016/j.scitotenv.2021.146660
- Chen X, Wang T, Qiu XH, Que CL, Zhang HXY, Zhang LN, Zhu T. Susceptibility of individuals with chronic obstructive pulmonary disease to air pollution exposure in Beijing, China: A case-control panel study (COPDB). Science of the Total Environment, 2020, 717, 137285. https://doi.org/10.1016/j.scitotenv.2020.137285
