焦炉工人尿中多环芳烃代谢物与SAHH活力及H19基因表达的关系

Association among urinary polycyclic aromatic hydrocarbons metabolites,SAHH activity and H19 expression in coke oven workers

目的探讨焦炉工人尿中多环芳烃(polycyclic aromatic hydrocarbons,PAHs)暴露与S-腺苷高半胱氨酸水解酶(S-adenosylhomocysteine hydrolase,SAHH)活力及长链非编码RNA H19基因表达的关系。方法于2019年9月,在太原市某焦化厂通过完全随机抽样的方法,选取焦炉作业满1年的男性工人146人,问卷调查法收集其个人基本信息,并采集血样和尿样。采用高效液相色谱(high performance liquid chromatography,HPLC)-荧光检测法检测尿中4种PAHs代谢物2-羟基芴、2-羟基萘、9-羟基菲、1-羟基芘的水平;HPLC-紫外检测法检测血浆中S-腺苷蛋氨酸(S-adenosylmethionine,SAM)和S-腺苷高半胱氨酸(S-adenosylhomocysteine,SAH)的含量,通过计算比值得到SAHH活力值;反转录PCR法测定H19基因表达水平。将尿中2-羟基芴、2-羟基萘、9-羟基菲、1-羟基芘水平根据四分位数(P25、P50、P75)各分为Q1、Q2、Q3、Q4组,采用多元logistic回归、趋势检验和限制性立方样条分析PAHs代谢物与SAHH活力、H19基因表达的关系及其剂量反应。结果焦炉工人年龄中位数为39.60岁,工龄中位数为20.38年,尿中2-羟基芴、2-羟基萘、9-羟基菲和1-羟基芘水平分别为0.29、0.74、0.09、0.06μg/mmol Cr。不同1-羟基芘水平组间,工人尿中2-羟基芴、2-羟基萘、9-羟基菲水平差异均有统计学意义(P<0.05)。校正了年龄、工龄、吸烟、饮酒及2-羟基芴、2-羟基萘、9-羟基菲水平后,SAHH活力随尿中1-羟基芘水平的升高而降低(OR=0.63,95%CI:0.41~0.98,P=0.038),表现为非线性关系(P_(非线性)=0.030);H19基因表达水平随尿中1-羟基芘浓度的升高而升高(OR=1.51,95%CI:1.03~2.19,P=0.033),存在线性关系(P_(趋势)=0.058)。其他3种尿中代谢物与SAHH活力、H19基因表达的关系均无统计学意义(P>0.05)。结论尿中1-羟基芘水平可能是焦炉工人SAHH活力降低、H19基因表达升高的危险因素。

Objective To investigate the relationship of polycyclic aromatic hydrocarbons(PAHs)exposure,S-adenosylhomocysteine hydrolase(SAHH)activity and long noncoding RNA H19 gene expression in the urine of coke oven workers.Methods In September 2019,in a coking plant in Taiyuan City,146 male workers who had worked in coke oven operations for one year were selected through a completely random sampling method,and their basic personal information was collected by questionnaire survey,and blood and urine samples were collected.The levels of 4 PAHs metabolites 2-hydroxfluorene(2-FLU),2-hydroxynaphthalene(2-NAP),9-hydroxyphenanthren(9-PHE),and 1-hydroxypyrene(1-OHP)in urine were detected by high performance liquid chromatography(HPLC)-fluorescence detection method.HPLC-UV detection method was used to detect the content of S-adenosylmethionine(SAM)and S-adenosylhomocysteine(SAH)in plasma,and the SAHH activity value was obtained by calculating the ratio.Reverse transcription PCR method was used to determine the H19 gene expression level.Urine levels of 2-FLU,2-NAP,9-PHE,and 1-OHP were divided into Q1,Q2,Q3,and Q4 groups according to quartiles(P25,P50,P75).Regression,trend test and restricted cubic splines were used to analyze the relationship among PAHs metabolites,SAHH activity,H19 gene expression and their dose-response.Results The median age of coke oven workers was 39.60 years old,the median length of service was 20.38 years,and the urinary levels of 2-FLU,2-NAP,9-PHE,and 1-OHP were 0.29,0.74,0.09,and 0.06μg/mmol Cr,respectively.The levels of 2-FLU,2-NAP and 9-PHE in the urine of workers were significantly different between groups with different 1-OHP levels(P<0.05).After adjusting for age,length of service,smoking,drinking,and levels of 2-FLU,2-NAP and 9-PHE,SAHH activity decreased with the increase of urinary 1-OHP level(OR=0.63,95%CI:0.41-0.98,P=0.038),showing a nonlinear relationship(P_(nonlinear)=0.030).H19 gene expression increased with the increase of urinary 1-OHP level(OR=1.51,95%CI:1.03-2.19,P=0.033),there was a linear relationship(P_(trend)=0.058).The relationship between the other three metabolites in urine and SAHH activity and H19 gene expression was not statistically significant(P>0.05).Conclusion Urinary 1-OHP level may be a risk factor for decreased SAHH activity and increased H19 gene expression in coke oven workers.