基于Wnt信号通路探讨氟砷混合暴露的生物暴露限值

doi:10.13287/j.1001-9332.201901.023

应用生态学报 ›› 2019, Vol. 30 ›› Issue (1): 37-42.doi: 10.13287/j.1001-9332.201901.023

基于Wnt信号通路探讨氟砷混合暴露的生物暴露限值

曾奇兵¹,徐玉艳¹,涂成龙¹,喻仙²,杨鋆²,洪峰^1,3*

¹贵州医科大学环境污染与疾病监控教育部重点实验室, 贵阳 550025;
²贵阳市疾病预防控制中心, 贵阳 550001;
³贵州医科大学公共卫生学院, 贵阳 550025

收稿日期:2018-10-08 修回日期:2018-11-06 出版日期:2019-01-20 发布日期:2019-01-20
通讯作者: hongfeng-73@163.com
作者简介:曾奇兵, 男, 1985年生, 副教授. 主要从事氟砷联合中毒发病机制及防制研究. E-mail: 178945324@qq.com
基金资助:
本文由国家自然科学基金项目(81472927)和贵州省科学技术基金项目(黔科合J字[2015]2010)资助

Biological exposure limits caused by co exposure to fluoride and arsenic based on Wnt signaling pathway

ZENG Qi-bing¹, XU Yu-yan¹, TU Cheng-long¹, YU Xian², YANG Jun², HONG Feng^1,3*

¹Ministry of Education Key Laboratory of Environmental Pollution Monitoring and Disease Control, Guizhou Medical University, Guiyang 550025, China;
²Guiyang Centers for Diseases Control and Prevention, Guiyang 550001, China;
³School of Public Health, Guizhou Medical University, Guiyang 550025, China

Received:2018-10-08 Revised:2018-11-06 Online:2019-01-20 Published:2019-01-20
Supported by:
This work was supported by the National Natural Science Foundation of China (81472927) and the Science and Technology Foundation of Guizhou Province, China (QianKH-J[2015]2010).

摘要/Abstract

摘要： 慢性氟砷联合中毒是全世界的一个重大公共卫生问题,影响着数千万人.目前该病病因清楚,但发病机制未明,且无特效治疗方法,因此,早期预防尤为重要.生物暴露限值旨在探讨外源化学物引起机体有害效应的最高容许浓度.为了探讨氟砷混合暴露的生物暴露限值(BEL),本研究通过比较对照及氟砷联合暴露地区环境介质中的氟、砷含量,分析氟、砷与Wnt信号通路关键蛋白的剂量-效应及剂量-反应关系,利用基准剂量法估算氟砷混合暴露的生物暴露限值.结果表明: 氟砷联合暴露地区煤、黏土、室内空气、室外空气、辣椒、大米中的氟含量以及煤、黏土、室外空气、辣椒、大米中的砷含量均高于对照;随着氟、砷暴露水平的增加,糖原合酶激酶3β(GSK3β)、β-连环蛋白(β-catenin)含量以及Wnt/β连环蛋白信号通路拮抗蛋白(DKK1)、GSK3β、β-catenin的异常检出率逐渐增加,但DKK1含量显著降低;基于Wnt信号通路,氟砷混合暴露的生物暴露限值UF为0.52 mg·g^-1Cr,UAs为6.59 μg·g^-1Cr.本研究对于早期预防氟砷联合中毒引起的机体损伤具有重要的指导意义.

关键词: 基准剂量, 氟, Wnt信号通路, 生物暴露限值, 砷

Abstract: Chronic fluoride-arsenic combined poisoning is a global public health problem. While the cause of the disease is clear, the pathogenesis is unknown. Given that there is no specific treatment, early prevention is particularly important. Biological exposure limits are designed to investigate the maximum allowable concentration of harmful effects from exogenous chemicals. To explore the biological exposure limits for mixed exposures of fluoride and arsenic, we compared the contents of fluorine and arsenic in the environmental media of the control and fluoride-arsenic combined exposure areas and analyzed the dose-effect and dose-response relationship between fluoride, arsenic and the key proteins of Wnt signaling pathways. The benchmark dose method was used to estimate the biological exposure limit for fluoride-arsenic combined exposure. The results showed that the content of fluoride in coal, clay, indoor air, outdoor air, chili and rice, as well as arsenic content in coal, clay, outdoor air, chili and rice was higher than that of the control. With the increase of fluoride and arsenic exposure levels, the glycogen synthase kinase 3β (GSK3β), β-catenincontents and the prevalence of Wnt/β-catenin signaling pathway antagonistic protein Dickkopf-1 (DKK1), GSK3β, Beta-catenin (β-catenin) gradually increased, but the content of DKK1 significantly decreased. Based on the Wnt signaling pathway, the biological exposure limit for fluoride-arsenic combined exposure was urinary fluoride of 0.52 mg·g^-1 creatinine and urinary arsenic of 6.59 mg·g^-1 creatinine. Our results had important guiding significance for early prevention of body damage caused by fluoride-arsenic combined poisoning.

Key words: arsenic, fluoride, biological exposure limit, benchmark dose., Wnt signaling pathway

曾奇兵,徐玉艳,涂成龙,喻仙,杨鋆,洪峰. 基于Wnt信号通路探讨氟砷混合暴露的生物暴露限值[J]. 应用生态学报, 2019, 30(1): 37-42.

ZENG Qi-bing, XU Yu-yan, TU Cheng-long, YU Xian, YANG Jun, HONG Feng. Biological exposure limits caused by co exposure to fluoride and arsenic based on Wnt signaling pathway[J]. Chinese Journal of Applied Ecology, 2019, 30(1): 37-42.

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基于Wnt信号通路探讨氟砷混合暴露的生物暴露限值

Biological exposure limits caused by co exposure to fluoride and arsenic based on Wnt signaling pathway

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