铅离子导致神经胶质细胞毒性的代谢组学机制

doi:10.3976/j.issn.1002-4026.2019.06.005

山东科学 ›› 2019, Vol. 32 ›› Issue (6): 26-33.doi: 10.3976/j.issn.1002-4026.2019.06.005

铅离子导致神经胶质细胞毒性的代谢组学机制

穆岩^a，李丽丽^b，马双双^b，宋月^a，王泉博^a*

齐鲁工业大学（山东省科学院）山东省分析测试中心 a. 环境与健康免疫研究室; b. 山东省中药质量控制技术重点实验室，山东济南 250014

收稿日期:2019-08-12 出版日期:2019-12-20 发布日期:2019-12-06
通信作者: 王泉博（1986—），男，博士，助理研究员，研究方向为生物分析化学。E-mail: qbwang1@qq.com
作者简介:穆岩（1987—）,男，博士，助理研究员，研究方向为药理学。E-mail:my3634@163.com
基金资助:
山东省科学院青年基金（2018QN001）;山东省自然科学基金三院联合基金（ZR2016YL006）

Metabolomics mechanism of Pb²⁺induced cytotoxicity to microglial cells

MU Yan^a, LI Li-li^b, MA Shuang-shuang^b, SONG Yue^a, Wang Quan-bo^a*

a. Laboratory of Immunology for Environment and Health; b. Shandong Key Laboratory of TCM Quality Control Technology, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, China

Received:2019-08-12 Online:2019-12-20 Published:2019-12-06

摘要/Abstract

摘要： 以神经胶质细胞为细胞模型，观察铅离子暴露细胞形态变化、细胞存活率和凋亡，并采用UPLCQTOF液质联用技术测定铅离子暴露的神经胶质细胞和正常细胞代谢物水平。结果显示：10 μmol/L 铅离子可引起神经胶质细胞的形态发生显著变化，细胞存活率降低，凋亡比例上升；多达973个潜在代谢物水平变化大于1.5倍（在P<0.05时）；主成分分析显示铅离子暴露组和正常对照组细胞具有显著不同的聚类趋势；差异代谢物的通路富集分析显示铅离子显著改变神经胶质细胞中谷氨酰胺和谷氨酸盐代谢、抗坏血酸/醛酸代谢、丁酸盐代谢以及谷胱甘肽代谢等多个涉及氧化还原等功能的重要代谢通路。铅离子生物毒性作用机制研究可为缓解铅毒性药物研发提供实验基础和理论参考。

关键词: 铅毒性, 神经胶质细胞, 代谢组学, 液质联用仪

Abstract: The microgial cells were used as a model to study the morphological changes, cell viability, and apoptosis induced by Pb²⁺. The metabolite levels in the microglial cells exposed to Pb²⁺or solvent were measured using UPLC-QTOF mass spectrometry. The results show that a concentration of 10 μmol/L Pb²⁺caused significant morphology changes, decreased cell viability, and increased the cell apoptosis of microglial cells. UPLC-QTOF mass spectrometry data showed that almost 973 potential metabolite levels were significantly changed with more than 1.5 folds (P < 0.05). Principal component analysis showed that Pb²⁺ exposure group and the normal control group had obviously different clustering trends.The pathway enrichment analysis of differential metabolites showed that Pb²⁺ significantly changed several key metabolism pathways involved in oxidation and reduction function, including glutamine/glutamate metabolism, ascorbate/aldarate metabolism, butanoate metabolism, and glutathione metabolism. These results provide an experimental basis and theoretical reference for the toxicity mechanism and alleviation drugs development of Pb²⁺.

Key words: Pb²⁺ toxicity, microglial cell, metabolomics, UPLC-QTOF mass spectrometry

中图分类号:

穆岩, 李丽丽, 马双双, 宋月, 王泉博. 铅离子导致神经胶质细胞毒性的代谢组学机制[J]. 山东科学, 2019, 32(6): 26-33.

MU Yan, LI Li-li, MA Shuang-shuang, SONG Yue, Wang Quan-bo. Metabolomics mechanism of Pb²⁺induced cytotoxicity to microglial cells[J]. Shandong Science, 2019, 32(6): 26-33.

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铅离子导致神经胶质细胞毒性的代谢组学机制

Metabolomics mechanism of Pb²⁺induced cytotoxicity to microglial cells

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铅离子导致神经胶质细胞毒性的代谢组学机制

Metabolomics mechanism of Pb2+induced cytotoxicity to microglial cells

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Metabolomics mechanism of Pb²⁺induced cytotoxicity to microglial cells