空气细颗粒物及组分暴露通过血浆miRNA表达致动脉硬化的固定群组研究

Ambient fine particulate matter (PM2.5) exposure could cause arterial stiffness, but the underlying mechanisms are largely unknown. Recent studies on miRNA have showed their involvements in the occurrence and development of arterial stiffness, however, the potential role of miRNA was never investigated in the pathogenesis of arterial stiffness caused by exposure to PM2.5 and its components. We plan to measure the 72-hour individual exposure to metals and polycyclic aromatic hydrocarbons (PAHs) from air, urinary concentrations of metals and PAHs metabolites, and 5 candidate plasma miRNAs which are related to arterial stiffness in 143 community residents from the previous panel study at Summer, Autumn, and Winter sampling. Personal exposure to PM2.5 for 72 h and arterial stiffness indices (including brachial-ankle pulse wave velocity and ankle brachial index) of the 143 volunteers were obtained in the 3 rounds of sampling. We will examine the dose-response relationships of personal exposure to PM2.5 and its components with arterial stiffness, miRNAs with personal exposure to PM2.5 and its components, miRNAs with arterial stiffness, as well as the mediation role of miRNAs in the association between personal exposure to PM2.5 and its components and arterial stiffness. Our results will provide scientific evidence for investigating the role of miRNAs in arterial stiffness caused by exposure to PM2.5 and its components.

空气细颗粒物（PM2.5）污染可导致动脉硬化损伤，但机制仍不清楚。miRNA在动脉硬化的发生发展中起着重要调控作用，然而，miRNA在PM2.5及其组分暴露致动脉硬化损伤中的作用尚未见报道。本项目利用课题组刚完成的固定群组，通过测定其中143名个体夏、秋、冬三季采集的连续72小时的空气滤膜和尿液中金属、多环芳烃代谢产物，以及血浆中5种与动脉硬化损伤相关的候选miRNAs表达水平，结合个体已经检测的PM2.5浓度和动脉硬化指标（肱踝脉搏波传导速度和踝臂指数），分析个体PM2.5及组分、血浆miRNAs水平和动脉硬化指标之间的剂量-反应关系，以及miRNAs在PM2.5及组分暴露致动脉硬化损伤中的介导效应，为探讨miRNAs的变化在PM2.5及组分暴露致动脉硬化损害的作用提供科学依据。

空气细颗粒物及组分暴露与动脉硬化的关联及其可能的生物学机制并不清楚。本项目通过测定武汉市143名社区居民夏、秋、冬三季每季连续4天的尿液中23种金属、10种多环芳烃（PAHs）代谢产物，以及血浆中5种动脉硬化损伤相关的miRNAs表达水平，结合已经检测的个体72 h 空气细颗粒物（PM2.5）和动脉硬化指标——肱踝脉搏波传导速度（baPWV）和踝臂指数（ABI），系统地分析了个体PM2.5及主要组分（金属、PAHs）暴露、血浆miRNAs表达、动脉硬化的剂量-反应关系，以及miRNAs在PM2.5及组分暴露致动脉硬化损伤中的介导效应。取得了如下主要成果：1、不同滞后天数中个体PM2.5、PAHs暴露与动脉硬化损伤指标（baPWV、ABI）之间均无统计学关联。2、4天平均的尿钛、尿钴与ABI呈负相关，且呈倒“J”型的剂量-反应关系。滞后第0天以及4天平均的钛暴露与外周动脉疾病 （peripheral artery disease，PAD）的患病风险增加呈正相关。3、滞后第0天的尿锰与miR-125b，尿3-羟基菲、4-羟基菲与miR-146a，尿2-羟基菲与miR-21，滞后第2天以及4天平均的尿2-羟基芴、9-羟基菲与miR-146a均呈正相关。而miR-146a的升高与ABI的下降呈显著的剂量-反应关系，尚未发现miR-146a在金属、PAHs暴露致动脉硬化损伤中的介导效应。研究结果为进一步揭示PM2.5及组分暴露致动脉硬化损害的风险评估提供了基础研究资料和早期生物标志物。