氧化应激在高分子多环芳烃代谢物与不明原因复发性流产的中介效应  

Mediating effect of oxidative stress on metabolites of high-molecular-weight PAHs and unexplained recurrent spontaneous abortion

作　　者：吕春贤 李丹丹 章正 程千喜 李亚伟[1] 宋皓璨 陆一夫[1,3] 李永刚 赵峰[1] LYU Chun-xian;LI Dan-dan;ZHANG Zheng;CHENG Qian-xi;LI Ya-wei;SONG Hao-can;LU Yi-fu;LI Yong-gang;ZHAO Feng(China CDC Key Laboratory of Environment and Population Health/National Institute of Environmental Health,Chinese Center for Disease Control and Prevention,Beijing 100021,China;Fengtai District Center for Disease Control and Prevention,Beijing;Center for Global Health,School of Public Health,Nanjing Medical University;Institute of Health Inspection and Testing,Hubei Provincial Center for Disease Control and Prevention)

机构地区：[1]中国疾病预防控制中心环境与人群健康重点实验室/中国疾病预防控制中心环境与健康相关产品安全所,北京100021 [2]北京市丰台区疾病预防控制中心 [3]南京医科大学公共卫生学院全球健康中心 [4]湖北省疾病预防控制中心卫生检验检测研究所

出　　处：《环境卫生学杂志》2024年第4期295-302,317,共9页JOURNAL OF ENVIRONMENTAL HYGIENE

基　　金：国家卫生健康委员会公共卫生专项计划(131031108000160004);国家重点研发计划(2022YFA0806600)。

摘　　要：目的探索高分子量多环芳烃(high-molecular-weight polycyclic aromatic hydrocarbons,HMW PAHs)代谢物与不明原因复发性流产(unexplained recurrent spontaneous abortion,URSA)的关联及氧化应激生物标志物在其中的中介效应。方法采用病例-对照研究方法,招募2018年4—10月在首都医科大学附属北京妇产医院就诊的URSA患者为病例组,自愿到该院门诊进行人工流产的正常妊娠孕妇为对照组。共纳入156名研究对象,病例组81名,对照组75名。采集研究对象随机中段尿50 mL,采用气相色谱-串联质谱检测6种HMW PAHs(3-羟基荧蒽(3-Hydroxyfluoranthene,3-BF)、1-羟基芘(1-Hydroxypyrene,1-PYR)、6-羟基■(6-Hydroxychrysene,6-CHR)、3-羟基■(3-Hydroxychrysene,3-CHR)、3-羟基苯并[a]蒽(3-Hydroxybenz[a]anthracene,3-BAA)、3-羟基苯并[a]芘(3-Hydroxybenzo[a]pyrene,3-BAP)),采用酶联免疫吸附测定法检测8-羟基脱氧鸟苷(8-hydroxy-2-deoxyguanosine,8-OHdG)和8-异前列腺素F2α(8-isoprostaglandin F2α,8-iso-PGF2α)2种氧化应激生物标志物浓度。采用多因素Logistic回归模型计算HMW PAHs代谢物以及氧化应激生物标志物和URSA的关联关系。采用多重线性回归模型计算HMW PAHs代谢物与氧化应激生物标志物的关联,并采用中介效应模型计算氧化应激生物标志物在HMW PAHs代谢物与URSA之间的中介效应。结果研究对象平均年龄为(31.91±4.68)岁,BMI平均水平为(22.74±4.19)kg/m 2,平均初潮年龄为(13.13±1.32)岁,病例组和对照组的初潮年龄、教育水平存在显著差异。病例组的3-BAA和8-iso-PGF2α水平高于对照组(P<0.05)。与尿中3-BAA的Q1组相比,Q4组的URSA患病风险增加,OR(95%CI)为4.95(1.11,10.91),P_(趋势)<0.05。3-BAA与8-OHdG和8-iso-PGF2α均呈正向关联,与尿中3-BAA的Q1组相比,Q4组的8-OHdG和8-iso-PGF2α的变化水平(95%CI)分别为0.75(0.38,1.13)和0.84(0.52,1.15)。中介效应分析显示:8-iso-PGF2α部分介导了3-BAA与URSA的关联,中介效应占比为31.8%。�Objective To investigate the association between the metabolites of high-molecular-weight polycyclic aromatic hydrocarbons(HMW PAHs)and unexplained recurrent spontaneous abortion(URSA)and the mediating effect of oxidative stress biomarkers.Methods Using the case-control study method,the patients with URSA who attended Beijing Obstetrics and Gynecology Hospital Affiliated to Capital Medical University from April to October 2018 were enrolled as the case group,and normal pregnant women who voluntarily went to the outpatient service of the hospital for artificial abortion were enrolled as the control group.A total of 156 subjects were included,with 81 in the case group and 75 in the control group.The 50 mL random midstream urine samples were collected from all subjects,and gas chromatography-tandem mass spectrometry was used to measure the metabolites of 6 HMW PAHs(3-Hydroxyfluoranthene(3-BF),1-Hydroxypyrene(1-PYR),6-Hydroxychrysene(6-CHR),3-Hydroxychrysene(3-CHR),3-Hydroxybenz[a]anthracene(3-BAA),and 3-Hydroxybenzo[a]pyrene(3-BAP)).Enzyme-linked immunosorbent assay was used to measure the concentrations of 2 oxidative stress biomarkers,including 8-hydroxy-2-deoxyguanosine(8-OHdG)and 8-isoprostaglandin F2α(8-iso-PGF2α).The multiple logistic regression model was used to assess the association between the metabolites of HMW PAHs and oxidative stress biomarkers with URSA.The multiple linear regression model was used to analyze the association between the metabolites of HMW PAHs and oxidative stress biomarkers.The mediating effect analysis was used to investigate the mediating effect of oxidative stress biomarkers between the metabolites of HMW PAHs and URSA.Results The subjects had a mean age of(31.91±4.68)years,a mean body mass index of(22.74±4.19)kg/m 2,and a mean age of menarche of(13.13±1.32)years,and there were significant differences in the age of menarche and educational level between the case group and the control group.The case group had significantly higher levels of 3-BAA and 8-iso-PGF2αthan the contro

关 键 词：多环芳烃 不明原因复发性流产 中介效应分析 氧化应激生物标志物 

分 类 号：R12[医药卫生—环境卫生学]