高通量检测技术在化学物神经毒性评估中的应用

    Application of high-throughput detection techniques in the assessment of chemical neurotoxicity

    • 摘要: 高通量检测技术已逐渐成为化学物神经毒性评估中的一类高效的检测手段, 具有良好的应用前景。本文综述了空间组学检测、高内涵成像、高通量测序和计算毒理学四种高通量检测技术在神经系统毒性评估研究中的应用现状, 并对其优势及发展前景进行了分析讨论。空间组学通过整合代谢组、转录组、蛋白质组等多组学检测方法, 有助于解析代谢物和基因表达的空间分布特征, 促进对神经毒性机制的深入理解。高内涵成像技术通过高通量筛选出细胞表型变化、发现敏感生物标志物, 实现对化学物质神经毒性的高效评估。高通量测序作为一类大规模并行技术, 涵盖RNA测序、表观基因组测序、单细胞测序及全基因组测序等手段, 解析基因表达谱与表观遗传修饰, 为揭示神经毒性作用机制和识别潜在生物标志物提供重要支持。计算毒理学通过构建有害结局路径, 从高通量的角度实现了对神经毒物的毒性评估和风险管理, 成为了一种替代动物实验的神经毒性检测手段。

       

      Abstract: High-throughput detection techniques have become a class of efficient assays for assessing chemical neurotoxicity, showing significant promise for future applications. This paper reviews the current status of the application of four high-throughput detection technologies, namely spatial omics detection, high-content imaging, high-throughput sequencing, and computational toxicology, in neurotoxicity assessment studies. Their respective advantages and development prospects are analyzed and discussed. Spatial omics, by integrating multiple omics approaches such as metabolomics, transcriptomics, and proteomics, helps to elucidate the spatial distribution of metabolites and gene expression, thereby promoting a deeper understanding of neurotoxicity mechanisms. High-content imaging technology enables the efficient assessment of chemical neurotoxicity by identifying cellular phenotypic changes and discovering sensitive biomarkers in a high-throughput manner. High-throughput sequencing, as a class of large-scale parallel technologies, encompasses RNA sequencing, epigenomic sequencing, single-cell sequencing, and whole-genome sequencing for the analysis of gene expression profiles and epigenetic modifications, providing critical support for elucidating neurotoxicity mechanisms and identifying potential biomarkers. Computational toxicological approaches facilitate the toxicity assessment and risk management of neurotoxicants from a high-throughput perspective by constructing adverse outcome pathways, thereby serving as an alternative to animal experiments for neurotoxicity detection.

       

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