林杨, 尹京晶, 孟庆玉, 王振杰, 吴难, 张丽雅, 王婷, 王艳华, 段化伟. 大气颗粒物暴露儿童血清多环芳烃加合物与白细胞miR-638的剂量-效应关系[J]. 环境与职业医学, 2021, 38(10): 1099-1105. DOI: 10.13213/j.cnki.jeom.2021.21214
引用本文: 林杨, 尹京晶, 孟庆玉, 王振杰, 吴难, 张丽雅, 王婷, 王艳华, 段化伟. 大气颗粒物暴露儿童血清多环芳烃加合物与白细胞miR-638的剂量-效应关系[J]. 环境与职业医学, 2021, 38(10): 1099-1105. DOI: 10.13213/j.cnki.jeom.2021.21214
LIN Yang, YIN Jingjing, MENG Qingyu, WANG Zhenjie, WU Nan, ZHANG Liya, WANG Ting, WANG Yanhua, DUAN Huawei. Dose-effect relationship between serum polycyclic aromatic hydrocarbon adducts and leukocyte miR-638 in children exposed to ambient particulate matter[J]. Journal of Environmental and Occupational Medicine, 2021, 38(10): 1099-1105. DOI: 10.13213/j.cnki.jeom.2021.21214
Citation: LIN Yang, YIN Jingjing, MENG Qingyu, WANG Zhenjie, WU Nan, ZHANG Liya, WANG Ting, WANG Yanhua, DUAN Huawei. Dose-effect relationship between serum polycyclic aromatic hydrocarbon adducts and leukocyte miR-638 in children exposed to ambient particulate matter[J]. Journal of Environmental and Occupational Medicine, 2021, 38(10): 1099-1105. DOI: 10.13213/j.cnki.jeom.2021.21214

大气颗粒物暴露儿童血清多环芳烃加合物与白细胞miR-638的剂量-效应关系

Dose-effect relationship between serum polycyclic aromatic hydrocarbon adducts and leukocyte miR-638 in children exposed to ambient particulate matter

  • 摘要: 背景

    大气颗粒物(PM)及其多环芳烃(PAH)组分的暴露可以导致外周血白细胞microRNA(miRNA)表达改变,引起机体氧化应激和炎症反应等早期损伤。儿童是颗粒物暴露的敏感人群,然而颗粒物对儿童血液中的miRNA影响研究较少。

    目的

    探讨颗粒物暴露儿童血清PAH- 白蛋白加合物与白细胞miR-638表达的剂量- 效应关系。

    方法

    选取大气颗粒物高暴露区域的162名寄宿制学校儿童为高暴露组,低暴露区域108名寄宿制学校儿童为低暴露组。收集两个地区全年的PM2.5、PM10浓度数据,通过定点采样确定校园内PM2.5浓度及其附着的苯并a 芘(BaP)浓度,依据尿可替宁浓度评估儿童的烟草暴露水平,检测血清中反式二氢二醇环氧苯并a 芘(BPDE)- 白蛋白加合物浓度,评估PAH长期暴露水平;实时荧光定量PCR法检测外周血白细胞miR-638表达水平。线性回归模型分析不同亚组白细胞miR-638表达差异和血清BPDE- 白蛋白加合物与白细胞miR-638表达水平剂量- 效应关系。

    结果

    大气颗粒物高暴露组儿童PM2.5(79.00 μg·m-3)、PM10(175.00 μg·m-3)年均暴露水平以及血清BPDE- 白蛋白加合物(82.41±20.12)nmol·L-1水平高于低暴露组46.00 μg·m-3,82.00 μg·m-3,(64.84±14.26)nmol·L-1P < 0.05)。暴露评估结果表明PM2.5与BaP(r=0.691,P < 0.001)呈正相关。高暴露组白细胞miR-638相对表达水平MP25P75):1.00(0.62,1.53)均高于低暴露组MP25P75):0.70(0.47,1.20)(P < 0.05)。线性回归模型分析结果显示,校正年龄、性别、尿可替宁、体重指数(BMI)z- 评分和白细胞计数水平后,儿童血清中BPDE- 白蛋白加合物水平每增加一个四分位数间距(IQR)(27.09 nmol·L-1),白细胞miR-638水平增加24.56%(P < 0.001);其中高暴露组儿童血清BPDE- 白蛋白加合物水平每增加一个IQR(25.95 nmol·L-1),白细胞miR-638水平增加19.28%(P=0.003)。亚组分析发现,男生和女生血清BPDE- 白蛋白加合物水平每增加一个IQR(27.34、28.84 nmol·L-1),白细胞miR-638水平分别增加20.60%(P=0.007)和34.57%(P=0.012);在正常体重组的儿童中,血清BPDE- 白蛋白加合物水平每增加一个IQR(24.74 nmol·L-1),白细胞miR-638水平增加26.89%(P < 0.001);在尿可替宁未检出组儿童中,血清BPDE- 白蛋白加合物每增加一个IQR(25.06 nmol·L-1),miR-638水平增加23.78%(P < 0.001)。

    结论

    大气颗粒物中PAH组分可致儿童外周血白细胞miR-638水平升高,血清中BPDE- 白蛋白加合物与白细胞miR-638表达水平存在较好的剂量- 效应关系。

     

    Abstract: Background

    Exposure to particulate matter (PM) and polycyclic aromatic hydrocarbon composition can influence the expression of microRNA (miRNA) in leukocytes, which can induce oxidative stress, inflammatory response, and immune response. Children are sensitive to PM exposure, but there are few studies on the changes of miRNA in their peripheral blood in association with PM.

    Objective

    The study aims to investigate potential dose-effect relationship between polycyclic aromatic hydrocarbon-albumin adducts in serum and miR-638 in leukocytes among children exposed to PM.

    Methods

    A total of 162 children from boarding schools in an area with high PM exposure were selected as the high-PM exposure group, while 108 children from boarding schools in an area with low PM exposure were as the low-PM exposure group. The annual levels of PM2.5 and PM10 in the two areas were collected. The concentrations of PM2.5 and benzoapyrene (BaP) in PM2.5 on campus were determined at fixed monitoring sites. Tobacco exposure was assessed according to the concentration of urinary cotinine. The long-term exposure level of PAH was assessed by serum benzoapyrene diol epoxide (BPDE)-albumin adducts. The expression of miR-638 was detected by real-time quantitative PCR. Linear regression model was used to analyze the differences in miR-638 among different subgroups and the dose-effect relationship between serum BPDE-albumin adducts and miR-638 level in leukocytes.

    Results

    The concentrations of annual PM2.5 (79.00μg·m-3), annual PM10 (175.00μg·m-3), and serum BPDE-albumin adducts (82.41±20.12) nmol·L-1 in the high-PM exposure group were higher than those in the low-PM exposure group 46.00 μg·m-3, 82.00 μg·m-3, (64.84±14.26) nmol·L-1(P < 0.001). PM2.5 level was positively correlated with BaP level (r=0.691, P < 0.001). The level of leukocyte miR-638 M (P25, P75): 1.00(0.62, 1.53) in the high-PM exposure group was significantly higher than that in the low-PM exposure M (P25, P75): 0.70 (0.47, 1.20) (P < 0.05). After adjusting for age, sex, urinary cotinine, body mass index (BMI) z-scores, and white blood cell counts, the results of linear regression model showed that an interquartile range (IQR, 27.09 nmol·L-1) increase in serum BPDE-albumin adducts was associated with 24.56% (P < 0.001) increment of miR-638 among children; an IQR (25.95 nmol·L-1) increase in serum BPDE-albumin adducts was associated with 19.28%(P=0.003) increase of miR-638 in the high-PM exposure group. After stratification, with each IQR (27.34, 28.84, 24.74, 25.06 nmol·L-1) increase of serum BPDE-albumin adducts, the expression levels of miR-638 increased by 20.60% (P=0.007) in boys, 34.57% (P=0.012) in girls, 26.89% (P < 0.001) in normal weight children, and 23.78% (P < 0.001) in the children without urinary cotinine detected.

    Conclusion

    PAH components in PM could induce elevated miR-638 in leukocytes among selected school children. There is a significant dose-effect relationship between serum BPDE-albumin adducts and miR-638 in leukocytes.

     

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