芳香烃受体在双酚A所致斑马鱼胚胎发育毒性中的作用研究
Study on the role of AhR in the developmental toxicity of zebrafish embryos induced by bisphenol A
[目的]本文以斑马鱼作为模式动物,研究AhR在BPA所致斑马鱼胚胎发育毒性中的作用。 [方法]本研究将斑马鱼胚胎随机分为8组进行染毒,分别为DMSO对照组、AhR抑制剂(CH)对照组、BPA暴露组(1、5、25 μM)、CH+BPA(1、5、25 μM)组。染毒时间为受精后2-96小时,分别观察斑马鱼胚胎的死亡率、孵化率、畸形率、心率、体长及运动能力。并通过荧光定量PCR方法检测AhR、心脏发育、神经发育相关基因的表达情况。 [结果]BPA暴露组斑马鱼胚胎出现孵化延迟、心率下降、死亡率增加、畸形率升高、体长缩短以及运动距离下降的现象(P < 0.05)。AhR抑制剂CH+BPA组斑马鱼的体长、心率及运动能力均有所恢复(P < 0.05)。荧光定量PCR结果表明, BPA组AhR相关基因(ahr2、cyp1a1和cyp1b1)显著上调(P < 0.05);心脏发育关键基因(nkx2.5和sox9b)、神经发育相关基因(elavl3、gfap、mbp和syn2a)均显著下调(P < 0.05)。AhR抑制剂CH+BPA组上述基因表达与单纯BPA暴露组相比均有明显改善(P < 0.05)。 [结论]AhR信号通路的活化与斑马鱼胚胎期暴露于BPA导致发育毒性有关。
[Objective] This research uses zebrafish as a model animal to study the role of AhR in the developmental toxicity of zebrafish embryos induced by BPA. [Methods] In this study, zebrafish embryos were randomly divided into 8 groups for exposure: DMSO control group, AhR inhibitor CH223191 (CH) control group, BPA exposure group (1 μM, 5 μM, 25 μM), CH+BPA (1 μM, 5 μM, 25 μM) groups. The exposure period was from 2hpf to 96hpf. The mortality, hatching rate, malformation rate, heart rate, body length and locomotor ability of zebrafish embryos were observed. The expression of AhR-related genes (ahr2, cyp1a1, cyp1b1), heart development key genes (nkx2.5, sox9b), and neurodevelopment key genes (elavl3, gfap, mbp, syn2a) were detected by fluorescence quantitative PCR. [Results]Zebrafish embryos in the BPA exposure group had delayed hatching, decreased heart rate, increased mortality and malformation rate, shortened body length, and decreased movement distance. The differences were statistically significant (P < 0.05). The body length, heart rate and locomotor ability of zebrafish in the CH+BPA group recovered, and the differences were statistically significant (P < 0.05). But the hatching rate, heart rate and mortality rate did not affect. Fluorescence quantitative PCR results showed that AhR-related genes (ahr2, cyp1a1, and cyp1b1) in the BPA group were significantly up-regulated (P < 0.05); key genes for cardiac development (nkx2.5 and sox9b), and genes related to neurodevelopment (elavl3, gfap, mbp, and syn2a) were significantly down-regulated (P < 0.05). The expressions were all down-regulated to varying degrees, and the differences were statistically significant (P < 0.05). The expression of the above genes in the CH+BPA group was significantly improved compared with the BPA exposure group alone, and the difference was statistically significant (P < 0.05). [Conclusion]The activation of AhR signaling pathway is related to the developmental toxicity caused by exposure to BPA in zebrafish embryos.
何梦婷、王伟、许洁、张洁
环境生物学生物科学现状、生物科学发展环境污染、环境污染防治
双酚A芳香烃受体芳香烃受体抑制剂斑马鱼发育毒性
BPAAhRZebrafishAhR inhibitorDevelopmental toxicity
何梦婷,王伟,许洁,张洁.芳香烃受体在双酚A所致斑马鱼胚胎发育毒性中的作用研究[EB/OL].(2021-01-22)[2025-08-16].http://www.paper.edu.cn/releasepaper/content/202101-63.点此复制
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