Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Nanjing, 210009, China.
Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University, Nanjing, 210009, China.
J Appl Toxicol. 2018 Sep;38(9):1177-1194. doi: 10.1002/jat.3629. Epub 2018 May 3.
Recently, the increasing number of bio-safety assessments on cadmium-containing quantum dots (QDs) suggested that they could lead to detrimental effects on the central nervous system (CNS) of living organisms, but the underlying action mechanisms are still rarely reported. In this study, whole-transcriptome sequencing was performed to analyze the changes in genome-wide gene expression pattern of rat hippocampus after treatments of cadmium telluride (CdTe) QDs with two sizes to understand better the mechanisms of CdTe QDs causing toxic effects in the CNS. We identified 2095 differentially expressed genes (DEGs). Fifty-five DEGs were between the control and 2.2 nm CdTe QDs, 1180 were between the control and 3.5 nm CdTe QDs and 860 were between the two kinds of CdTe QDs. It seemed that the 3.5 nm CdTe QD exposure might elicit severe effects in the rat hippocampus than 2.2 nm CdTe QDs at the transcriptome level. After bioinformatics analysis, we found that most DEG-enriched Gene Ontology subcategories and Kyoto Encyclopedia of Genes and Genomes pathways were related with the immune system process. For example, the Gene Ontology subcategories included immune response, inflammatory response and T-cell proliferation; Kyoto Encyclopedia of Genes and Genomes pathways included NOD/Toll-like receptor signaling pathway, nuclear factor-κB signaling pathway, tumor necrosis factor signaling pathway, natural killer cell-mediated cytotoxicity and T/B-cell receptor signaling pathway. The traditional toxicological examinations confirmed the systemic immune response and CNS inflammation in rats exposed to CdTe QDs. This transcriptome analysis not only revealed the probably molecular mechanisms of CdTe QDs causing neurotoxicity, but also provided references for the further related studies.
最近,越来越多的关于含镉量子点(QDs)的生物安全评估表明,它们可能对生物体的中枢神经系统(CNS)产生有害影响,但潜在的作用机制仍很少报道。在这项研究中,进行了全转录组测序,以分析大鼠海马体全基因组基因表达模式在两种尺寸的碲化镉(CdTe)量子点处理后的变化,以更好地理解 CdTe QDs 在中枢神经系统中引起毒性作用的机制。我们鉴定了 2095 个差异表达基因(DEGs)。在对照组和 2.2nm CdTe QDs 之间有 55 个 DEGs,在对照组和 3.5nm CdTe QDs 之间有 1180 个 DEGs,在这两种 CdTe QDs 之间有 860 个 DEGs。似乎 3.5nm CdTe QD 暴露在转录组水平上比 2.2nm CdTe QDs 更可能在大鼠海马体中引起严重影响。经过生物信息学分析,我们发现大多数 DEG 富集的基因本体论亚类和京都基因与基因组百科全书途径与免疫系统过程有关。例如,基因本体论亚类包括免疫反应、炎症反应和 T 细胞增殖;京都基因与基因组百科全书途径包括 NOD/Toll 样受体信号通路、核因子-κB 信号通路、肿瘤坏死因子信号通路、自然杀伤细胞介导的细胞毒性和 T/B 细胞受体信号通路。传统的毒理学检查证实了暴露于 CdTe QDs 的大鼠的全身免疫反应和中枢神经系统炎症。这项转录组分析不仅揭示了 CdTe QDs 引起神经毒性的可能分子机制,还为进一步的相关研究提供了参考。