尿金属混合物与脂质氧化损伤的分子流行病学研究  

Molecular epidemiological study of urinary metal mixtures and lipid oxidative damage

作　　者：袁慧阁 王艳华[1] 张丽雅 张雪薇 阿丽米热·阿不力克木 周彩兰 段化伟[1] 牛勇[1] YUAN Hui-ge;WANG Yan-hua;ZHANG Li-ya;ZHANG Xue-wei;ALIMIRE·Abulikemu;ZHOU Cai-lan;DUAN Hua-wei;NIU Yong(National Institute for Occupational Health and Poison Control,Chinese Center for Disease Control and Prevention,Beijing 100050,China)

机构地区：[1]中国疾病预防控制中心职业卫生与中毒控制所,北京100050

出　　处：《环境卫生学杂志》2023年第10期713-723,共11页JOURNAL OF ENVIRONMENTAL HYGIENE

基　　金：国家自然科学基金(82073525、82103888);国家重点研发计划(2022YFC2503203);环境毒理学北京市重点实验室基金(2023hjd102)。

摘　　要：目的利用混合污染物统计学模型,探讨金属混合物中致机体脂质氧化损伤的主要毒性组分。方法选取768名钢铁冶炼厂工人为研究对象。电感耦合等离子体质谱法测定尿液中钒(V)、铬(Cr)、锰(Mn)、镍(Ni)、砷(As)、锶(Sr)、镉(Cd)、铅(Pb)、硒(Se)、钴(Co)、铜(Cu)和锌(Zn)12种金属浓度;酶联免疫吸附法测定尿8-异前列腺素F2α(8-iso-PGF2α)浓度;采用MDA-硫代巴比妥酸加合物法测定尿中丙二醛(MDA)浓度。应用贝叶斯核机器回归(BKMR)、分位数g计算回归,分析尿金属与尿8-iso-PGF2α和尿MDA水平的关联。结果BKMR分析结果显示,当所有尿金属浓度均处于第50百分位数(P_(50))时,金属混合暴露的总效应使尿8-iso-PGF2α和尿MDA水平升高(P<0.05)。当所有尿金属浓度处于P_(50)与处于P_(25)相比,尿8-iso-PGF2α水平增加36.72%、尿MDA水平增加34.24%。金属导致脂质氧化损伤的主要作用组分为Se、Cd、Zn,当其它尿金属分别固定在P_(25)、P_(50)、P_(75)时,尿Se浓度每增加一个四分位间距,尿8-iso-PGF2α水平分别增加30.7%、35.4%和41.2%;尿MDA水平分别增加35.3%、42.8%和54.7%。分位数g计算结果显示,金属混合物水平每增加25%,尿8-iso-PGF2α和尿MDA水平分别升高63.05%和61.23%。结论金属混合暴露可能会引起机体脂质氧化损伤标志物水平升高,其中Se、Cd、Zn效应更为显著。Objective To explore the main toxic components of metal mixtures in urine responsible for lipid oxidative damage based on the statistical model of mixed pollutants.Methods A total of 768 participants in a iron and steel smelting plant were recruited and their urine was collected.Urinary concentrations of vanadium(V),chromium(Cr),manganese(Mn),nickel(Ni),arsenic(As),strontium(Sr),cadmium(Cd),lead(Pb),selenium(Se),cobalt(Co),copper(Cu),and zinc(Zn)were determined by inductively coupled plasma mass spectrometry.The concentration of urinary 8-iso-prostaglandin F2α(8-iso-PGF2α)was measured by ELISA.The concentration of urinary malondialdehyde(MDA)was determined by the MDA-thiobarbituric acid adduct method.Bayesian kernel machine regression(BKMR)and quantile g-computation were performed to analyze the associations of urinary metals with urinary 8-iso-PGF2αand MDA levels.Results BKMR analysis showed that the total effect of mixed metal exposure increased the levels of 8-iso-PGF2αand MDA in urine(P<0.05)when all urinary metal concentrations were at the 50th percentile(P_(50)).Urinary 8-iso-PGF2αlevel increased by 36.72%and urinary MDA level increased by 34.24%when all urinary metal concentrations were at P_(50)as compared with P_(25).The main components in metal mixtures responsible for lipid oxidative damage were Se,Cd,and Zn.When other urinary metals were fixed at P_(25),P_(50),and P_(75),urinary 8-iso-PGF2αlevels increased by 30.7%,35.4%,and 41.2%and urinary MDA levels increased by 35.3%,42.8%,and 54.7%with each interquartile range increase in urinary Se.Quantile g-computation showed that 25%increase of the metal mixture levels resulted in 63.05%increase of urinary 8-iso-PGF2αand 61.23%increase of urinary MDA,respectively.Conclusion Exposure to metal mixture increases the levels of lipid oxidative damage,and the effects of Se,Cd,and Zn are more significant.

关 键 词：脂质氧化损伤 尿金属 贝叶斯核机器回归 分位数g计算 

分 类 号：R12[医药卫生—环境卫生学]