多环芳烃代谢物与健康老年人氧化应激标志物的关联研究

    Association of polycyclic aromatic hydrocarbons with oxidative stress markers in healthy elderly individuals

    • 摘要:
      目的 评估多环芳烃(polycyclic aromatic hydrocarbons, PAHs)单一暴露和混合暴露对健康老年人氧化应激标志物的影响, 识别影响氧化应激标志物的关键物质。
      方法 在山东省济南市招募76名60~69岁健康老年人开展定群研究, 于2018年9月—2019年1月开展5次人群流行病学调查, 对调查对象进行问卷调查并采集尿液和血液样本。采用气相色谱-串联质谱法测量尿液中6种PAHs代谢物, 包括1-羟基萘、2-羟基萘、2-羟基芴、3-羟基芴、2-羟基菲和1-羟基芘; 并采用高效液相色谱-串联质谱法测量2种氧化应激标志物, 包括8-羟基鸟苷和8-羟基脱氧鸟苷。应用线性混合效应模型、分位数g计算(quantile g-computation, qgcomp)和贝叶斯核机器回归(Bayesian kernel machine regression, BKMR)模型分析PAHs代谢物和氧化应激标志物的关联。
      结果 本研究共纳入76名健康老年人, 男女各半, 年龄为(65±3)岁, 体质指数为(25.12±2.49)kg/m2。1-羟基萘、2-羟基萘、2-羟基芴、3-羟基芴、2-羟基菲和1-羟基芘的中位数浓度分别为1.16、0.83、0.24、0.08、0.06和0.10 μg/L。8-羟基鸟苷和8-羟基脱氧鸟苷的中位数浓度分别为5.66和4.50 ng/mL。6种PAHs代谢物每增加1个单位(常用对数lg转化), 8-羟基鸟苷和8-羟基脱氧鸟苷的上升范围分别为20.88%~72.67%和13.32%~70.19%。qgcomp和BKMR结果均表明, PAHs代谢物混合暴露对8-羟基鸟苷和8-羟基脱氧鸟苷水平的总效应呈显著正相关, 其中2-羟基芴对氧化应激的影响最大。
      结论 PAHs单一暴露和混合暴露与老年人氧化应激水平存在关联, 其中2-羟基芴对氧化应激标志物的影响最显著。

       

      Abstract:
      Objective To evaluate the effects of single and mixed exposure to polycyclic aromatic hydrocarbons (PAHs) on oxidative stress markers in healthy elderly individuals, and to identify the key PAHs that affect oxidative stress markers.
      Methods A panel of 76 healthy elderly individuals aged 60-69 years was recruited in Jinan, Shandong Province, China to participate in five epidemiological surveys from September 2018 to January 2019. The participants' basic information was gathered using a questionnaire, and their urine and blood samples were collected. The urine samples were examined by gas chromatography-tandem mass spectrometry for six PAHs, including 1-hydroxynaphthalene (1-NAP), 2-hydroxynaphthalene (2-NAP), 2-hydroxyfluorene (2-FLUO), 3-hydroxyfluorene (3-FLUO), 2-hydroxyphenanthrene (2-PHEN), and 1-hydroxypyrene (1-PYR). The levels of oxidative stress markers, including 8-hydroxyguanosine (8-OHG) and 8-hydroxydeoxyguanosine (8-OHdG), were determined by high-performance liquid chromatography-tandem mass spectrometry. The relationship between the PAHs and the oxidative stress markers was assessed by using a linear mixed-effects model, quantile g-computation (qgcomp) regression model, and Bayesian kernel machine regression (BKMR) model.
      Results For the 76 included individuals (half male and half female), the mean age was 65±3 years, and the mean body mass index was 25.12±2.49 kg/m2. The median concentrations of 1-NAP, 2-NAP, 2-FLUO, 3-FLUO, 2-PHEN, and 1-PYR were 1.16, 0.83, 0.24, 0.08, 0.06, and 0.10 μg/L, respectively. The median concentrations of 8-OHG and 8-OHdG were 5.66 and 4.50 ng/mL, respectively. For every 10-fold increase in the six PAHs, the percent changes in 8-OHG and 8-OHdG levels were 20.88% to 72.67% and 13.32% to 70.19%, respectively. The qgcomp and BKMR models showed mixed PAHs exposure was significantly positively associated with the total effects on 8-OHG and 8-OHdG levels, with 2-FLUO contributing most to oxidative stress.
      Conclusion Exposure to PAHs, either individually or as a mixture, is associated with oxidative stress levels in healthy elderly individuals, in which 2-FLUO has the most significant effects on oxidative stress markers.

       

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