氧化应激在尼古丁与不明原因复发性流产的中介效应  

Mediating effect of oxidative stress on association between nicotine and unexplained recurrent spontaneous abortion

作　　者：李丹丹 孟中华[2] 曲英莉[1] 李园园 朱会卷 刘仲[2] 赵峰[1] LI Dandan;MENG Zhonghua;QU Yingli;LI Yuanyuan;ZHUHuijuan;LIU Zhong;ZHAO Feng(National Institute of Environmental Health,Chinese Center for Disease Control and Prevention,Beijing 100050,China;Physical and Chemical Laboratory,Shandong Jinan Center for Disease Control and Prevention,Jinan,Shandong 250021,China;Big Data Office,Beijing Tongzhou District Center for Disease Control and Prevention,Beijing 101199,China;Second Department of Chemical Drug Monitoring and Evaluation,Center for Drug Reevaluation,National Medical Products Administration,Beijing 100022,China)

机构地区：[1]中国疾病预防控制中心环境与健康相关产品安全所,北京100050 [2]山东省济南市疾病预防控制中心理化检验所,山东济南250021 [3]北京市通州区疾病预防控制中心大数据办公室,北京101199 [4]国家药品监督管理局药品评价中心化学药品监测和评价二部,北京100022

出　　处：《环境与职业医学》2022年第5期512-518,526,共8页Journal of Environmental and Occupational Medicine

基　　金：北京市自然科学基金项目(7182119)。

摘　　要：[背景]既往研究已证实,尼古丁暴露是流产的独立危险因素,然而关于尼古丁是否通过氧化应激引起不明原因复发性流产(URSA)尚不明确。[目的]探究氧化应激在尼古丁暴露与URSA之间的中介作用。[方法]采用1∶1配对的病例对照研究方法,选取2018年4—10月在首都医科大学附属北京妇产医院就诊的88名URSA患者作为病例组,既往无不良妊娠结局且去该医院门诊做人工流产的88名妊娠妇女作为对照组。采用酶联免疫吸附测定法分别测定尿中8-羟基脱氧鸟苷(8-OHd G)和8-异前列腺素F2α(8-iso-PGF2α)水平;采用气相色谱-质谱联用技术测定尿中尼古丁水平。采用多因素条件logistic回归模型分析尼古丁、8-OHd G和8-iso-PGF2α与URSA风险的关联,采用多元线性回归分析尼古丁与8-OHd G和8-iso-PGF2α的关联,并采用二分应变量中介模型探索氧化应激在尼古丁暴露对URSA影响的中介作用。[结果]病例组尿中尼古丁、8-OHd G和8-iso-PGF2α的质量分数中位数分别是7.78、4.84、44.10μg·g(肌酐校正),对照组分别是6.48、3.34、29.39μg·g–1(肌酐校正),病例组尿中尼古丁、8-OHd G和8-iso-PGF2α的质量分数均高于对照组(均P <0.05)。条件logistic回归结果显示:调整混杂因素后,与Q1组相比,尼古丁和8-iso-PGF2α的Q4组URSA的OR(95%CI)分别是4.20(1.33~13.29)和6.25(1.66~23.59);与8-OHd G的Q1组相比,Q2、Q3和Q4组URSA的OR(95%CI)分别是5.47(1.43~20.93)、4.24(1.28~14.07)和6.36(1.82~22.28)。多元线性回归结果显示:校正混杂因素后,病例组和对照组尿中尼古丁与8-OHd G质量分数均呈正向关联,b(95%CI)分别是0.76(0.67~0.86)和0.81(0.67~0.95),病例组和对照组尿中尼古丁与8-isoPGF2α质量分数均呈正向关联,b(95%CI)分别是0.65(0.55~0.75)和0.76(0.64~0.87)。二分应变量中介结果显示:8-iso-PGF2α在尼古丁内暴露水平与URSA之间的中介效应大小及其95%CI是1.518(0.749~2.311)。[结论]尼古丁内暴露是URSA[Background] Previous studies have confirmed that nicotine exposure is an independent risk factor for miscarriage, but it is not clear whether nicotine causes unexplained recurrent spontaneous abortion(URSA) through oxidative stress.[Objective] To explore potential mediating effect of oxidative stress on the relationship between nicotine exposure and URSA.[Methods] Using a 1∶1 matched case-control study, 88 patients with URSA visiting Beijing Obstetrics and Gynecology Hospital affiliated to Capital Medical University from April to October in 2018 were selected as the case group, and 88 pregnant women without adverse pregnancy outcomes and seeking induced abortion in the outpatient clinic of the same hospital were selected as the control group. The levels of 8-hydroxy-2’-deoxyguanosine(8-OHd G) and 8-iso-prostaglandin F2α(8-iso-PGF2α) in urine were determined by enzyme-linked immunosorbent assay, and the level of urinary nicotine was determined by gas chromatography-mass spectrometry. Conditional logistic regression was used to analyze the associations of nicotine, 8-OHd G, and 8-iso-PGF2α with the risk of URSA. Multiple linear regression was used to analyze the association of nicotine with 8-OHd G and 8-iso-PGF2α. The potential mediating effect of oxidative stress on URSA after nicotine exposure was explored by dichotomous mediating model.[Results] The median concentrations(creatinine corrected) of nicotine, 8-OHd G, and 8-iso-PGF2α in urine of the case group were 7.78,4.84, and 44.10 μg·g-1, respectively, while those of the control group were 6.48, 3.34, and 29.39 μg·g, respectively. The concentrations of nicotine, 8-OHd G, and 8-iso-PGF2α in urine of the case group were all higher than those of the control group(P < 0.05). The results of conditional logistic regression model showed that after adjusting selected confounding factors, compared with the Q1 groups of nicotine and 8-iso-PGF2α, the OR(95%CI) values of URSA in the Q4 groups were 4.20(1.33-13.29) and 6.25(1.66-23.59), respectively. Compar

关 键 词：尼古丁 不明原因复发性流产 中介效应 8-羟基脱氧鸟苷 8-异前列腺素F2Α 

分 类 号：R17[医药卫生—妇幼卫生保健]