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内分泌干扰化学物质对斑马鱼(Danio rerio)早期发育阶段与先天免疫系统相关基因转录的影响。

Effect of endocrine disrupting chemicals on the transcription of genes related to the innate immune system in the early developmental stage of zebrafish (Danio rerio).

机构信息

College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.

出版信息

Fish Shellfish Immunol. 2010 May-Jun;28(5-6):854-61. doi: 10.1016/j.fsi.2010.02.009. Epub 2010 Feb 11.

DOI:10.1016/j.fsi.2010.02.009
PMID:20153439
Abstract

Health concerns regarding the potential interference of endocrine disrupting chemicals (EDCs) in the immune system of wildlife and humans have increased in recent years. However, the effects of EDCs in aquatic systems on the immune system of fish species has only received limited attention. In the present study, we found that the mRNA levels of TNFalpha, IFN, IL-1beta, IL-8, CXCL-Clc, and CC-chemokine, which are closely related to the innate immune system, were affected in newly hatched zebrafish when exposed to EDCs, such as 17beta-estradiol, 17alpha-ethynyestradiol, permethrin, atrazine and nonylphenol at various concentrations (0.1, 0.5, 2.5 and 12.5 microg/l) for three days during the embryo stage. However, the different EDCs displayed different potentials to change innate immune-related gene transcription. Among the selected chemicals, permethrin (PM) and 17beta-estradiol (E2) (12.5 microg/l) significantly increased the mRNA levels of many cytokines, exhibiting their most prominent impacts on the innate immune system of zebrafish. In addition, it was found that the mixture of the above five chemicals (2.5 microg/l each) had a greater effect on innate immune system-related gene transcription in zebrafish than equal amounts of the single compound. Moreover, the genes (such as Bcl2, Ucp2 and iNOS) relating to reactive oxygen species (ROS) and nitrogen reactive free radical production were also influenced by some EDCs and their mixture. We suggest that heavy oxidative stress and the balance of nitric oxide (NO) production lead to death of immune cells. These results may provide an explanation of the possible mode how EDCs influence the innate immune system in zebrafish. Taken together, the results obtained in the present study clearly demonstrate that EDCs and their mixtures in aquatic systems will greatly influence the immune system in fish, suggesting that the effects of EDCs on fish should be associated with immune toxicity.

摘要

近年来,人们越来越关注内分泌干扰化学物质(EDCs)对野生动物和人类免疫系统的潜在干扰。然而,水生系统中 EDC 对鱼类免疫系统的影响仅受到有限的关注。在本研究中,我们发现,当暴露于不同浓度(0.1、0.5、2.5 和 12.5μg/l)的 EDC 如 17β-雌二醇、17α-乙炔雌二醇、氯菊酯、莠去津和壬基酚时,刚孵化的斑马鱼胚胎期的 TNFalpha、IFN、IL-1β、IL-8、CXCL-Clc 和 CC-趋化因子等与先天免疫系统密切相关的 mRNA 水平受到影响。然而,不同的 EDC 显示出不同的改变先天免疫相关基因转录的潜力。在所选择的化学物质中,氯菊酯(PM)和 17β-雌二醇(E2)(12.5μg/l)显著增加了许多细胞因子的 mRNA 水平,对斑马鱼先天免疫系统的影响最为显著。此外,发现上述五种化学物质(每种 2.5μg/l)的混合物对斑马鱼先天免疫系统相关基因转录的影响大于等量单一化合物的混合物。此外,一些 EDC 及其混合物还影响与活性氧(ROS)和氮活性自由基产生相关的基因(如 Bcl2、Ucp2 和 iNOS)。我们认为,严重的氧化应激和一氧化氮(NO)产生的平衡导致免疫细胞死亡。这些结果可能解释了 EDC 影响斑马鱼先天免疫系统的可能模式。总之,本研究结果清楚地表明,水生系统中的 EDC 及其混合物将极大地影响鱼类的免疫系统,表明 EDC 对鱼类的影响应与免疫毒性相关。

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