铅作业工人外周血线粒体DNA拷贝数与血铅水平的关系

龚士洋; 涂雨婷; 方延; 王团伟; 张光辉; 夏昭林

doi:10.13213/j.cnki.jeom.2018.17670

铅作业工人外周血线粒体DNA拷贝数与血铅水平的关系

Association between mitochondrial DNA copy number and lead level in peripheral blood among leadexposed workers

摘要

摘要:
目的探究铅蓄电池厂工人外周血线粒体DNA拷贝数（mitochondrial DNA copy number，mtDNAcn）与血铅水平（bloodlead level，BLL）之间的关系。

方法招募873名某铅蓄电池厂工人作为研究对象，根据岗位的铅暴露情况，其中193位无铅和其他职业有害因素暴露者，作为对照组；680位仅有铅暴露者，作为暴露组。采用问卷收集铅作业工人的一般情况，血常规检测其血液学参数，采用实时荧光定量PCR检测外周血相对mtDNAcn，并用石墨炉原子吸收光谱法检测BLL。采用广义线性回归、多项式广义线性回归和限制性立方样条回归方法进行统计学分析。

结果研究对象总人群BLL的中位数（四分位数间距）是218.90 μg/L（180.60 μg/L）；对照组为65.50 μg/L（44.20 μg/L），暴露组为251.00 μg/L（141.05 μg/L）。对照组红细胞计数、平均红细胞血红蛋白量、平均红细胞血红蛋白浓度和血红蛋白浓度的中位数（四分位数间距）分别是4.71×10¹²/L（0.77×10¹²/L）、29.20 pg（2.00 pg）、316.00 g/L（9.00 g/L）和139.00 g/L（26.00 g/L）；暴露组红细胞计数、平均红细胞血红蛋白量、平均红细胞血红蛋白浓度和血红蛋白浓度的中位数（四分位数间距）分别是4.83×10¹²/L（0.74×10¹²/L）、28.80 pg（2.00 pg）、313.00 g/L（10.00 g/L）和140.00 g/L（21.00 g/L）。与对照组相比，暴露组BLL升高（P < 0.01），红细胞计数、平均红细胞血红蛋白含量、平均红细胞血红蛋白浓度和血红蛋白浓度均降低，差异均有统计学意义（均b < 0且P < 0.05）；暴露组相对mtDNAcn降低，差异有统计学意义（b=-0.13，P=0.04）。在血铅8.90~275.86μg/L范围内随着BLL的上升，mtDNAcn有明显下降趋势（b=-0.0016，P < 0.01）；在血铅275.86~647.70μg/L范围内，mtDNAcn随BLL的上升呈上升的趋势（b=0.0000029，P=0.02）。

结论铅作业工人的BLL可以导致外周血mtDNAcn的变化，提示职业性铅暴露可能导致线粒体损伤和功能异常，mtDNAcn可能可以作为职业性铅暴露的潜在生物标志。

Abstract:
Objective To explore the association between mitochondrial DNA copy number (mtDNAcn) and blood lead level (BLL) in peripheral blood of lead-exposed workers.

Methods A total of 873 workers in a lead storage battery plant were recruited, including 193 workers without exposure to lead and other occupational risk factors (control group) and 680 workers only exposed to lead (exposure group). A questionnaire survey was conducted to collect general information. Hematological parameters were detected by routine blood test. Quantitative real-time PCR was performed to calculate relative mtDNAcn. BLL was determined by graphite-furnace atomic absorption spectrophotometry. The statistical methods of this study included generalized linear regression, polynomial generalized linear regression, and restricted cubic spline regression.

Results The medians (quartile ranges) of BLL were 218.90 μg/L (180.60 μg/L) among total workers, 65.50 μg/L (44.20 μg/L) in the control group, and 251.00 μg/L (141.05 μg/L) in the exposure group. In the control group, the medians (quartile ranges) of red blood cell (RBC) count, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and hemoglobin (Hb) concentration were 4.71×10¹²/L (0.77×10¹²/L), 29.20 pg (2.00 pg), 316.00 g/L (9.00 g/L), and 139.00 g/L (26.00 g/L), respectively. The corresponding indicators were 4.83×10¹²/L (0.74×10¹²/L), 28.80 pg (2.00 pg), 313.00 g/L (10.00 g/L), and 140.00 g/L (21.00 g/L) in the exposure group, respectively. Compared with the control group, the exposure group showed increased BLL (P < 0.01), and decreased RBC count, MCH, MCHC, and Hb concentration (bs < 0 and Ps < 0.05). The relative mtDNAcn of the exposure group was lower than that of the control group (b=-0.13, P=0.04). When BLL was in the range of 8.90-275.86 μg/L, the relative mtDNAcn decreased with in creasing BLL (b=-0.001 6, P < 0.01), but when BLL was in the range of 275.86-647.70 μg/L, the relative mtDNAcn increased with in creasing BLL (b=0.000 002 9, P=0.02).

Conclusion Peripheral blood mtDNAcn is associated with BLL in selected lead-exposed workers, suggesting that occupational le ad exposure could induce damage and dysfunction in mitochondria. Moreover, mtDNAcn has the potential to be a biomarker of le ad exposure.

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