环境浓度氧化石墨烯和多环芳烃复合暴露诱发成年斑马鱼脑组织的分子响应研究
Molecular Response in Adult Zebrafish Brain Induced by Environment-related Concentration Graphene Oxide and Polycyclic Aromatic Hydrocarbons
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摘要: 氧化石墨烯（graphene oxide，GO）是目前十分重要的人工纳米材料，且极有可能被排放到环境中。因而GO与环境中的共存污染物多环芳烃（polycyclic aromatic hydrocarbons，PAHs）对水生生物的复合暴露毒性及其相关机理值得进一步研究。使用成年斑马鱼为动物模型，选取水环境浓度的典型污染物16种优控PAHs与环境预测浓度的GO对成年斑马鱼进行21 d亚急性暴露，研究GO和PAHs复合暴露对成年斑马鱼脑组织的毒性效应及其分子机理。结果表明，GO暴露组和PAHs-GO复合暴露组在21 d的亚急性暴露中均不会诱发成年斑马鱼的死亡和畸形，但会降低斑马鱼脑组织细胞色素P4501B1酶（CYP1B1）和β-半乳糖苷酶（β-Gal）的含量；在分子水平上，0.1 mg·L-1 GO组（GO组）、5 μg·L-1 PAHs组（PAHs组）和0.1 mg·L-1 GO&5 μg·L-1 PAHs组（PAHs-GO组）诱发的差异基因数量和差异基因通路数量排序为PAHs组>GO-PAHs组>GO组。研究表明：（1）在环境预测浓度的GO与环境浓度PAHs对成年斑马鱼复合暴露时，对斑马鱼脑组织酶的影响GO占据主导地位；（2） PAHs-GO复合暴露组兼具GO和PAHs的分子毒性效应的特点，说明GO和PAHs在环境相关浓度下的复合暴露分子毒性值得注意；（3） GO组转录组氧化酶相关基因变化与酶含量结果相一致，暗示可以使用转录组来解释生物酶含量变化的分子机理。本文结果可为纳米材料与环境污染物的复合毒性效应和机理研究提供参考。Abstract: Currently, graphene oxide (GO), as an important engineering nanomaterial, has a high potential to enter the environment. Therefore, the combined ecological mechanism and health effects of GO and polycyclic aromatic hydrocarbons (PAHs, a coexisting pollutants) on aquatic organisms need further study. In this study, adult zebrafish was selected as animal model for sub-acute exposure toxic research of GO at predicted environment concentration and 16 priority PAHs (typical pollutants) at environment concentration after 21 d of exposure. Then, combined toxic effects and molecular mechanism of GO and PAHs on adult zebrafish brain were explored. Results showed that both GO and PAHs-GO groups didn't induce death and malformation in adult zebrafish during 21 d of subacute exposure, but decreased cytochrome P4501B1 (CYP1B1) and β-galactosidase (β-Gal) content in zebrafish brain. Based on differential expressed genes (DEGs) and altered function pathways induced by treatment groups, the alteration order at the molecular level induced by 0.1 mg·L-1 GO (GO group), 5 μg·L-1 PAHs (PAHs group), and 0.1 mg·L-1 GO & 5 μg·L-1 PAHs (PAHs-GO group) was PAHs group > PAHs-GO group > GO group. In summary, this study reveals that (1) GO play a dominant role in alteration of CYP1B1 and β-Gal content in adult zebrafish brain for 21 d exposure to GO and co-exposure to GO with PAHs; (2) PAHs-GO co-exposure group share a common characteristic in the toxic effects of both GO and PAHs group, indicating the potential toxicity induced by PAHs-GO at environmental related concentration co-exposure need to notice; (3) For GO group, the alteration of oxidase content were consistent with the transcriptomic result, indicating that transcriptomics may help explain the molecular mechanism of oxidase alteration induced by GO. The results of this study can provide a reference for the combined toxicity effect and mechanism of nanomaterials and environmental coexisting pollutants.
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Key words:
- graphene oxide /
- polycyclic aromatic hydrocarbons /
- zebrafish /
- sub-acute toxicity /
- transcriptome
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