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北京大学学报（医学版） ›› 2019, Vol. 51 ›› Issue (2): 307-314. doi: 10.19723/j.issn.1671-167X.2019.02.021

• 论著 • 上一篇    下一篇

铬酸盐低水平长期职业接触与劳动者早期健康效应

刘佳兴1,胡贵平1,赵琳1,张永明1,王丽2,贾光1,∆(),刘瑞祥3,冯慧敏1,徐华东1   

  1. 1. 北京大学公共卫生学院劳动卫生与环境卫生学系, 北京 100191
    2. 内蒙古包头医学院公共卫生学院劳动卫生与环境卫生学系, 内蒙古自治区包头 014040
    3. 内蒙古北方重工业集团有限公司医院, 内蒙古自治区包头 014010
  • 收稿日期:2017-03-22 出版日期:2019-04-18 发布日期:2019-04-26
  • 通讯作者: 贾光 E-mail:jiaguangjia@bjmu.edu.cn
  • 基金资助:
    国家自然科学基金(81573118);国家自然科学基金(81273043)

Early effects of low-level long-term occupational chromate exposure on workers’ health

Jia-xing LIU1,Gui-ping HU1,Lin ZHAO1,Yong-ming ZHANG1,Li WANG2,Guang JIA1,∆(),Rui-xiang LIU3,Hui-min FENG1,Hua-dong XU1   

  1. 1. Department of Occupational and Environmental Health, Peking University School of Public Health, Beijing 100191, China
    2. Department of Occupational and Environmental Health, School of Public Health, Baotou Medical College, Baotou, 014040, Inner Mongolia, China
    3. Inner Mongolia North Heavy Industry Group Co., Ltd. Hospital, Baotou 014010, Inner Mongolia, China
  • Received:2017-03-22 Online:2019-04-18 Published:2019-04-26
  • Contact: Guang JIA E-mail:jiaguangjia@bjmu.edu.cn
  • Supported by:
    the National Natural Science Foundation of China(81573118);the National Natural Science Foundation of China(81273043)

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摘要：

目的: 从肺功能、免疫毒性及遗传损伤方面综合探讨铬酸盐长期低水平职业接触对劳动者健康的影响,以期发现潜在的早期健康效应标志物。方法: 以内蒙古某职业卫生环境监测下长期符合国家标准的电镀企业22名铬酸盐接触工人和44名非铬酸盐接触工人为研究对象,问卷调查收集工人基本情况、吸烟饮酒史、疾病史等信息;分别采用便携式肺功能仪、电感耦合等离子体质谱法和胞滞分裂阻滞微核试验测定铬酸盐接触工人肺功能、全血铬(whole blood Cr, WB-Cr)和外周血淋巴细胞微核率(micronuclei frequency, MNF);采用流式微球阵列法检测两组工人血清细胞因子IL-1β、IL-6、IL-8、IL-10、IL-12P70和TNFα含量,分析铬酸盐接触对上述生物内暴露、肺功能、免疫应答、遗传损伤各指标的影响及不同损伤效应间的相关性。结果: (1)铬酸盐接触工人平均工龄为31年,WB-Cr浓度为1.11~4.19 μg/L,按中位数1.72 μg/L将铬酸盐接触者分为高暴露组和低暴露组,高暴露组平均WB-Cr水平(2.17 μg/L)高于低暴露组(1.58 μg/L)和健康人群参考值(1.74 μg/L, P<0.05);(2)肺功能检测发现10名(45.45%)铬酸盐接触工人出现单个或多个肺功能指标异常情况,其中大气道损伤指标呼气流量峰值(peak expiratory flow,PEF)与小气道损伤指标每分钟最大通气量(maximum ventilation volume,MVV)和FEF25%~75%分别与WB-Cr呈负相关(r=-0.53,P<0.05; r=-0.52, P<0.05; r=-0.44,P<0.05);(3)铬酸盐接触工人血清IL-1β,IL-6,IL-8和TNFα均高于对照人群(P<0.05), 且TNFα与WB-Cr间存在正相关,各细胞因子之间两两正相关(P<0.05);(4)铬酸盐接触工人淋巴细胞MNF平均为1.341%, 高于一般人群参考值0.436%(P<0.01),Poisson多元回归结果显示高暴露工人MNF高于低暴露工人,OR(95%CI)值为1.323(1.049,1.669);(5)多元线性回归结果显示肺功能指标用力呼气中段流量 (forced expiratory flow rate 25%~75%,FEF25%~75%)随TNFα升高而降低(P<0.05),未发现其他细胞因子、MNF、肺功能指标之间存在有统计学意义的相关性。结论: 长期低水平铬酸盐职业接触引起劳动者肺功能下降、免疫炎症反应、遗传损伤的发生,其中局部或全身炎症反应与肺功能下降有关。肺功能指标PEF、FEF25%~75%、MVV,血清细胞因子IL-1β、IL-6、IL-8、TNFα水平和外周血淋巴细胞微核率可能作为铬酸盐暴露的早期健康效应标志物。

关键词: 铬酸盐, 肺功能, 细胞因子, 微核率, 炎症反应, 遗传损伤

Abstract:

Objective: To explore the effects of low-level long-term occupational exposure to chromate on the health of workers, and the potential biomarkers of early health effects in terms of lung function, immune toxicity and genetic damage.Methods: A total of 22 chromate contact workers and 44 non-chromate contact workers from an electroplating enterprise with long-term occupational environment monitoring in line with the national standards in Inner Mongolia were investigated. The questionnaire survey was conducted to collect the basic situation, the history of smoking, drinking, diseases and so on. The portable lung function instrument, inductively coupled plasma mass spectrometry and cytokinesis-blocked micronucleus test were performed to measure the chromate contact workers’ lung function, whole blood Cr (WB-Cr) and micronuclei frequency (MNF) of peripheral blood lymphocytes respectively. The cytometric bead array was used to detect the levels of IL-1β, IL-6, IL-8, IL-10, IL-12P70 and TNFα in the serum among the two groups. The effects of chromate exposure on the above-mentioned indexes involved biological exposure, lung function, immune response and genetic damage, and their correlation were analyzed with different statistical methods.Results: (1) the average length of service for chromate contact workers was 31 years, and their concentration of WB-Cr was 1.11-4.19 μg/L. They were divided into high and low exposure groups according to the median of 1.72 μg/L. The WB-Cr in the high exposure group (2.17 μg/L) was higher than that in the low exposure group (1.58 μg/L) as well as the reference value of the healthy population (1.74 μg/L, P<0.05); (2) the lung function test showed 10 (45.45%) chromate exposure workers had single or multiple abnormal lung function indexes, among which large airway injury index PEF, and small airway injury indexes MVV and FEF25%-75% were all negatively correlated with WB-Cr (r=-0.53, P<0.05; r=-0.52, P<0.05; r=-0.44, P<0.05); (3) IL-1β, IL-6, IL-8 and TNFα in the serum of chromate contact workers were higher than those in the control group (P<0.05), and there was a positive correlation between TNFα and WB-Cr, and among these cytokines (P<0.05); (4) the average lymphocyte MNF in chromate contact workers was 1.341%, higher than the reference value of the general population (0.436%, P<0.01). Poisson regression analysis showed MNF in thehigh exposure group was higher than that in the low exposure group, OR (95%CI) =1.323 (1.049, 1.669); (5) multiple linear regression analysis showed that the lung function index FEF25%-75% decreased with the increase of TNFα (P<0.05), no significant correlation was found between other cytokines, MNF and lung function indexes.Conclusion: Long-term low-level occupational exposure to chromate can cause the decline of lung function, immune inflammatory reaction and genetic damage in workers, in which local or systemic inflammatory response is associated with decreased lung function. Lung function indexes PEF, FEF25%-75% and MVV, serum cytokines IL-1β, IL-6, IL-8, and TNFα, and peripheral blood lymphocyte MNF may be used as early health effects biomarkers of chromate exposure.

Key words: Chromate, Lung function, Cytokines, Micronuclei frequency, Inflammatory response, Genetic damage

中图分类号: 

  • R135

表1

铬酸盐接触组与对照组工人基本情况比较"

Characteristics Exposure (n=22) Control (n=44) Statistics value P
Age/yearsa 42.32±9.71 41.57±9.10 -0.103b 0.918
Gender, n(%) <0.001c 1.000
Male 21 (95.50%) 42 (95.50%)
Female 1 (4.50%) 2 (4.50%)
BMI/(kg/m2)a 26.24±3.19 25.13±2.89 1.428b 0.158
Duration of exposure/yearsd 31 (10-31) -
Smoking, n(%) 0.122c 0.797
Yes 11 (50.00%) 20 (45.50%)
No 11 (50.00%) 24 (54.50%)
Drinking, n(%) 5.126c 0.036
Yes 7 (31.80%) 27 (61.40%)
No 15 (68.2%) 17 (38.60%)

表2

铬酸盐接触工人全血铬水平分布情况"

Items Low exposure group, n=11 High exposure group, n=11 Total, n=22 Za Pb
WB-Cr/(μg/L)
P50(P25-P75)		 1.58
1.15-1.67		 2.17
1.87-3.42		 1.72
1.57-2.26		 -3.973 <0.001
Pb 0.003 0.004 0.445

表3

铬酸盐接触工人肺功能及其与全血铬相关性分析"

Indexes Test value/% Abnormal numbers (proportion) Reference rage/% r
FVC pred 95.33±14.84 1 (4.55%) ≥80 -0.06
FEV1 pred 99.86±11.42 1 (4.55%) ≥80 -0.35
FEV1/FVC 87.34±7.28 0 (0%) ≥70 -0.32
PEF pred 74.71±18.02 9 (40.91%) ≥80 -0.53*
MVV pred 101.90±14.52 1 (4.55%) ≥80 -0.52*
FEF25%-75%pred 98.52±21.94 2 (9.09%) ≥80 -0.44*

表4

铬酸盐接触组与对照组血清细胞因子比较"

Cytokines Exposure (n=22) Control (n=44) Zb P
IL-1β/(ng/L)a 0.61
(0.00-3.48)		 0.00
(0.00-0.00)		 -3.670 <0.001#
IL-6/(ng/L)a 11.20
(6.52-23.97)		 7.26
(3.79-15.10)		 -2.068 0.039*
IL-8/(ng/L)a 501.26
(351.09-797.77)		 138.38
(81.02-276.81)		 -4.911 <0.001#
TNFα/(ng/L)a 5.17
(2.29-10.99)		 1.84
(0.90-4.68)		 -2.802 0.005#

表5

WB-Cr、IL-1β、IL-6、IL-8和TNFα相关性分析"

r WB-Cr IL-1β IL-6 IL-8 TNFα
WB-Cr 1.00 0.07 0.03 0.11 0.44*
IL-1β - 1.00 0.78# 0.70# 0.53*
IL-6 - - 1.00 0.85# 0.43*
IL-8 - - - 1.00 0.45*
TNFα - - - - 1.00

表6

铬酸盐接触工人淋巴细胞微核率比较"

Group MNF/%, x?±s Ta P OR(95%CI)b P
Total, n=22 1.341±0.588 7.222 <0.001# 1.323
(1.049, 1.669)		 0.018*
High exposure group, n=11 1.545±0.584 6.304 <0.001#
Low exposure group, n=11 1.136±0.541 4.295 0.002#

表7

肺功能指标FEF25%~75%与细胞因子、BMI等多元线性回归分析结果"

Varible Β value S value β’ value P value
TNFα -1.754 0.444 -0.622 0.001#
BMI -2.092 1.037 -0.311 0.061
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