基于PBPK模型的大鼠体内镉分布的比较：联合暴露及单独暴露

蒋艳雪; 贾宜静; 晁思宏; 曹红斌

doi:10.7524/AJE.1673-5897.20160504001

1. 北京师范大学中药资源保护与利用北京市重点实验室, 北京 100082;

2. 北京师范大学地理科学学部, 北京 100875

作者简介: 蒋艳雪(1992-),女,博士研究生,研究方向为环境健康,E-mail:201431190020@mail.bnu.edu.cn

通讯作者: 曹红斌, E-mail: caohongbin@bnu.edu.cn

基金项目:

国家科技支撑计划“村镇环境评价与预警平台建设”基金资助项目(2012BAJ24B04)

中图分类号: X171.5

Comparison of Cadmium Distribution in Rats between Exposed to Individual Cadmium and Heavy Metals Mixture Based on PBPK Model

1. Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing 100082, China;

2. Falculty of Geographical Science, Beijing Normal University, Beijing 100875, China

Corresponding author: Cao Hongbin, caohongbin@bnu.edu.cn

Fund Project:

摘要: 环境中同时存在着多种重金属元素,联合暴露与单独暴露时,重金属在体内的蓄积分布情况也可能有所差异。为探究重金属元素(汞、铬、砷、铅)对镉(Cd)在体内分布的影响,建立了大鼠在Cd暴露下的药代动力学(PBPK)模型,并进行了包括Cd在内5种重金属的联合毒性实验,比较了Cd单独给药与重金属混合物给药2种方式下大鼠肝脏、肾脏中的Cd浓度水平。结果表明,联合暴露高(HgCl₂ 3.67 mg·kg^-1,NaAsO₂ 3.67 mg·kg^-1,CdCl₂ 10.55 mg·kg^-1,K₂Cr₂ O₇ 6.40 mg·kg^-1,Pb(OOCCH₃)₂·3H₂O 133.33 mg·kg^-1)、中(HgCl₂ 0.367 mg·kg^-1,NaAsO₂ 0.367 mg·kg^-1,CdCl₂ 1.055 mg·kg^-1,K₂Cr₂O₇ 0.640 mg·kg^-1,Pb(OOCCH₃)₂·3H₂O 13.333 mg·kg^-1)、低(HgCl₂ 0.0367 mg·kg^-1,NaAsO₂ 0.0367 mg·kg^-1,CdCl₂ 0.1055 mg·kg^-1,K₂ Cr₂O₇ 0.0640 mg·kg^-1,Pb(OOCCH₃)₂ ·3H₂ O 1.3333 mg·kg^-1)剂量组大鼠肝脏中Cd浓度分别为13.37、0.78和0.06 μg·g^-1;肾脏中Cd浓度分别为14.41、1.64和0.15 μg·g^-1。与对照组相比,暴露组中Cd浓度有显著升高,且不同剂量组之间均有显著性差异。同剂量Cd单独暴露的PBPK模拟结果显示,肝脏及肾脏中的Cd浓度水平落在联合毒性实验结果的浓度范围内,初步推断其他4种重金属的联合暴露并没有影响Cd在大鼠肾脏和肝脏中的浓度分布。

Abstract: The distribution in vivo of metals mixture might be different from that of individual metals. In order to explore the influence of four metals (mercury, chromium, arsenic and lead) on the distribution of cadmium (Cd) in vivo, a physiologically based pharmacokinetic model (PBPK) was constructed to simulate the absorption, distribution, metabolism and excretion (ADME) of Cd in rats exposed to individual Cd. The levels of Cd in liver and kidney exposed to metals mixture were obtained from a joint toxicity experiment. The experiment results showed that the concentrations of Cd in liver in high (HgCl₂ 3.67 mg·kg^-1, NaAsO₂ 3.67 mg·kg^-1, CdCl₂ 10.55 mg·kg^-1, K₂Cr₂ O₇ 6.40 mg·kg^-1, Pb(OOCCH₃)₂·3H₂O 133.33 mg·kg^-1), medium (HgCl₂ 0.367 mg·kg^-1, NaAsO₂ 0.367 mg·kg^-1, CdCl₂ 1.055 mg·kg^-1, K₂Cr₂O₇ 0.640 mg·kg^-1, Pb(OOCCH₃)₂·3H₂O 13.333 mg·kg^-1) and low (HgCl₂ 0.0367 mg·kg^-1, NaAsO₂ 0.0367 mg·kg^-1, CdCl₂ 0.1055 mg·kg^-1, K₂ Cr₂O₇ 0.0640 mg·kg^-1, Pb(OOCCH₃)₂ ·3H₂ O 1.3333 mg·kg^-1) dose groups were 13.37, 0.78 and 0.06 μg·g^-1, respectively; and those in kidney were 14.41, 1.64 and 0.15 μg·g^-1, respectively. There were significant differences between the control group and exposure groups. The simulated concentrations of Cd in liver and kidney were in the range of the corresponding experimental concentrations. It is preliminarily inferred that the co-exposure with other four heavy metals had no obvious influence on Cd distribution in liver and kidney of rats.

Key words:

基于PBPK模型的大鼠体内镉分布的比较：联合暴露及单独暴露

通讯作者: 曹红斌, E-mail: caohongbin@bnu.edu.cn

作者简介: 蒋艳雪(1992-),女,博士研究生,研究方向为环境健康,E-mail:201431190020@mail.bnu.edu.cn
1. 北京师范大学中药资源保护与利用北京市重点实验室, 北京 100082;

2. 北京师范大学地理科学学部, 北京 100875

收稿日期: 2016-05-04

基金项目:

国家科技支撑计划“村镇环境评价与预警平台建设”基金资助项目(2012BAJ24B04)

关键词:

Comparison of Cadmium Distribution in Rats between Exposed to Individual Cadmium and Heavy Metals Mixture Based on PBPK Model

Corresponding author: Cao Hongbin, caohongbin@bnu.edu.cn

1. Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing 100082, China;

2. Falculty of Geographical Science, Beijing Normal University, Beijing 100875, China

Received Date: 2016-05-04

Fund Project:

Keywords:

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