School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Laboratory of Health Technology Assessment , Fudan University , Shanghai 200032 , China.
Shanghai Key Laboratory of Meteorology and Health , Shanghai 200030 , China.
Environ Sci Technol. 2018 Aug 7;52(15):8785-8791. doi: 10.1021/acs.est.8b01295. Epub 2018 Jul 19.
Little is known regarding the molecular mechanisms behind respiratory inflammatory response induced by ozone. We performed a longitudinal panel study with four repeated measurements among 43 young adults in Shanghai, China from May to October in 2016. We collected buccal samples and measured the fractional exhaled nitric oxide (FeNO) after 3-day personal ozone monitoring. In buccal samples, we measured concentrations of inducible nitric oxide synthase (iNOS) and arginase (ARG), and DNA methylation of NOS2A and ARG2. We used linear mixed-effect models to analyze the effects of ozone on FeNO, two enzymes and their DNA methylation. A 10 ppb increase in ozone (lag 0-8 h) was significantly associated with a 3.89% increase in FeNO, a 36.33% increase in iNOS, and a decrease of 0.36 in the average methylation (%5mC) of NOS2A. Ozone was associated with decreased ARG and elevated ARG2 methylation, but the associations were not significant. These effects were more pronounced among allergic subjects than healthy subjects. The effects were much stronger when using personal exposure monitoring than fixed-site measurements. Our study demonstrated that personal short-term exposure to ozone may result in acute respiratory inflammation, which may be mainly modulated by NOS2A hypomethylation in the arginase-nitric oxide synthase pathway.
目前对于臭氧诱导呼吸道炎症反应的分子机制知之甚少。我们在中国上海进行了一项纵向面板研究，共有 43 名年轻人参与，研究时间为 2016 年 5 月至 10 月，共进行了四次重复测量。我们采集了口腔样本，并在 3 天的个人臭氧监测后测量了呼出气一氧化氮（FeNO）的分数。在口腔样本中，我们测量了诱导型一氧化氮合酶（iNOS）和精氨酸酶（ARG）的浓度，以及 NOS2A 和 ARG2 的 DNA 甲基化。我们使用线性混合效应模型来分析臭氧对 FeNO、两种酶及其 DNA 甲基化的影响。臭氧浓度增加 10 个 ppb（滞后 0-8 小时）与 FeNO 增加 3.89%、iNOS 增加 36.33%以及 NOS2A 的平均甲基化（%5mC）减少 0.36 显著相关。臭氧与 ARG 减少和 ARG2 甲基化升高有关，但关联不显著。在过敏受试者中，这些关联比在健康受试者中更为明显。与使用固定点位测量相比，使用个人短期暴露监测时，这些效应更为显著。我们的研究表明，个人短期暴露于臭氧可能导致急性呼吸道炎症，这可能主要通过精氨酸酶-一氧化氮合酶途径中的 NOS2A 低甲基化来调节。
