基于代谢组学技术的金刚烷胺胁迫刺参的毒性作用机制研究
Research on Toxicity Mechanism of Amantadine on Apostichopus japonicus Revealed by Metabonomics
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摘要: 本研究基于非靶向代谢组学方法，分析了暴露于100 μg·L-1金刚烷胺下96 h的刺参代谢物组成及含量变化，以探究金刚烷胺对刺参肠道组织毒性及其相关分子机制。代谢组学结果表明，与对照组相比，金刚烷胺胁迫下，刺参肠道代谢物发生改变，共有115种差异表达代谢物，其主要功能分为二肽、类固醇、嘌呤和嘧啶。差异代谢物功能通路的富集结果表明，氨基酸代谢、脂质代谢、信号转导、核苷酸代谢和内分泌系统等生物过程受到显著影响。根据筛选出的差异代谢物的生理功能及其涉及的代谢通路分析，发现刺参信号传导和能量代谢功能受到干扰，可能由于腺苷和单磷酸腺苷(AMP)含量下降；睾酮和牛磺鹅去氧胆酸(TCDCA)含量下降可能对刺参的性别分化和胆固醇代谢产生影响；甘氨酸和脯氨酸含量上升可能是刺参胶原蛋白的降解造成的。本研究探究了金刚烷胺对刺参肠道组织毒性作用的分子机制及刺参的响应调控机制，为后期深入研究毒性机制提供理论依据。Abstract: To explore the toxicity of amantadine on intestinal tissue of Apostichopus japonicus and the related molecular mechanisms, the composition and content of metabolites were analyzed based on non-targeted metabolomics methods after the sea cucumbers were exposed to 100 μg·L-1 amantadine for 96 h. Metabolomics results showed that intestinal metabolites of A. japonicus were changed under amantadine stress, and there were 115 differentially expressed metabolites compared with the control group, whose main functions were dipeptide, steroid, purine and pyrimidine. The KEGG enrichment analysis showed that biological processes were significantly affected, such as amino acid metabolism, lipid metabolism, signal transduction, nucleotide metabolism and the endocrine system. According to the physiological functions of the selected differential metabolites and the metabolic pathways involved, it was found that the signal transduction and energy metabolism were disturbed, possibly due to the decrease of adenosine and adenosine monophosphate (AMP) content. The decrease in testosterone and taurochenodeoxycholic acid (TCDCA) content affected sex differentiation and cholesterol metabolism of A. japonicus. The increase in glycine and proline content might be caused by the degradation of the collagen of A. japonicus. This research explored the molecular mechanism of amantadine on intestinal tissue and the response regulation mechanism of A. japonicus, and provided the theoretical basis for further research on the toxic mechanism of amantadine.
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Key words:
- amantamine /
- Apostichopus japonicas /
- metabolomics /
- differential metabolite /
- metabolic pathway
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