• 中国中文核心期刊
  • 中国科学引文数据库核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
高级检索

基于代谢组学的水杨酸钠对HEI-OC1细胞损伤作用机制

何明哲, 彭英, 王广基, 阿基业, 郑亦文, 孙建国

何明哲, 彭英, 王广基, 阿基业, 郑亦文, 孙建国. 基于代谢组学的水杨酸钠对HEI-OC1细胞损伤作用机制[J]. 中国药科大学学报, 2021, 52(5): 566-572. DOI: 10.11665/j.issn.1000-5048.20210508
引用本文: 何明哲, 彭英, 王广基, 阿基业, 郑亦文, 孙建国. 基于代谢组学的水杨酸钠对HEI-OC1细胞损伤作用机制[J]. 中国药科大学学报, 2021, 52(5): 566-572. DOI: 10.11665/j.issn.1000-5048.20210508
HE Mingzhe, PENG Ying, WANG Guangji, A Jiye, ZHENG Yiwen, SUN Jianguo. Mechanism of sodium salicylate-induced damage to HEI-OC1 cells based on metabonomics[J]. Journal of China Pharmaceutical University, 2021, 52(5): 566-572. DOI: 10.11665/j.issn.1000-5048.20210508
Citation: HE Mingzhe, PENG Ying, WANG Guangji, A Jiye, ZHENG Yiwen, SUN Jianguo. Mechanism of sodium salicylate-induced damage to HEI-OC1 cells based on metabonomics[J]. Journal of China Pharmaceutical University, 2021, 52(5): 566-572. DOI: 10.11665/j.issn.1000-5048.20210508

基于代谢组学的水杨酸钠对HEI-OC1细胞损伤作用机制

基金项目: 国家重点研发计划“政府间国际科技创新合作”重点专项资助项目(No.2017YFE0109600)

Mechanism of sodium salicylate-induced damage to HEI-OC1 cells based on metabonomics

Funds: This study was supported by the National Key Research and Development Program for Intergovernmental Cooperation in International Science and Technology Innovation (No.2017YFE0109600)
  • 摘要: 基于LC-Q-TOF/MS技术探究水杨酸钠对小鼠HEI-OC1毛细胞样细胞中内源性代谢的影响。首先采用不同浓度的水杨酸钠处理HEI-OC1细胞,使用CCK-8法检测细胞存活率的变化。然后观察不同干预时间下水杨酸钠对细胞形态的影响,并利用代谢组学技术进行研究,筛选组间差异代谢产物,分析相关的代谢通路。结果表明,水杨酸钠能够显著抑制HEI-OC1细胞的存活率,且随着浓度的增加,抑制作用增强。同时水杨酸钠能够使细胞形态拉长,并在停止给药后恢复正常。水杨酸钠处理HEI-OC1细胞后共筛选出乳清酸、尿苷、天冬氨酸等18种差异代谢物,主要涉及丙氨酸、天冬氨酸和谷氨酸代谢及嘧啶代谢这两条可能的代谢通路。综上所述,本研究通过代谢组学技术评价了水杨酸钠对HEI-OC1细胞的作用,可为水杨酸钠耳毒性及耳鸣的发生发展研究提供新思路。
    Abstract: The effect of sodium salicylate on the endogenous metabolism of hair cell-like cells (HEI-OC1).of mice was analyzed based on liquid chromatography-quadrupole time of flight mass spectrometry (LC-Q-TOF/MS).Firstly, HEI-OC1 cells were treated with different concentrations of sodium salicylate, and cell survival was examined by the CCK-8 method. Next, sodium salicylate was administered for different duration to observe the changes in cell morphology. Inter-group differential metabolites were screened out, and the associated metabolic pathways were analyzed based on metabonomic technology.Results showed that sodium salicylate could significantly inhibit the survival rate of HEI-OC1 cells, and that, as the concentration increased, the inhibitory effect became stronger. Also, the cell morphology could be elongated after administration and return to normal after withdrawal.Eighteen differential metabolites such as orotic acid, uridine and aspartic acid were screened out after treatment of sodium salicylate, which mainly involving two possible metabolic pathways, namely the metabolism of alanine, aspartic acid and glutamic acid, and that of pyrimidine.In summary, the application of metabolomics technology to evaluate the effect of sodium salicylate on hair cells from the microscopic perspective can provide new ideas for the study of sodium salicylate ototoxicity and development of tinnitus.
  • [1] . Curr Med Res Opin,2011,27(8):1635-1643.
    [2] Bhatt JM,Lin HW,Bhattacharyya N. Prevalence,severity,exposures,and treatment patterns of tinnitus in the United States[J]. JAMA Otolaryngol Head Neck Surg,2016,142(10):959-965.
    [3] Galazyuk A,Brozoski TJ. Animal models of tinnitus:a review[J]. Otolaryngol Clin North Am,2020,53(4):469-480.
    [4] Li SH,Han DY,Yang WY,et al. Research progress on the ototoxicity mechanism of sodium salicylate[J]. J Audiol Speech Pathol(听力学及言语疾病杂志),2001,9(3):174-176.
    [5] Steffens DC,Wei Jiang,Krishnan KR,et al. Metabolomic differences in heart failure patients with and without major depression[J]. J Geriatr Psychiatry Neurol,2010,23(2):138-146.
    [6] Li WW,Yang Y,Wang SC,et al. Research progress of cellular metabolomics[J]. J Nanjing Univ Tradit Chin Med(南京中医药大学学报),2017,33(2):187-192.
    [7] Lu Z,Li S,Sun R,et al. Hirsutella sinensis treatment shows protective effects on renal injury and metabolic modulation in db/db mice[J]. Evid Based Complement Alternat Med,2019,2019:4732858.
    [8] Wang W,Cai Q,Zhou F,et al. Impaired pentose phosphate pathway in the development of 3D MCF-7 cells mediated intracellular redox disturbance and multi-cellular resistance without drug induction[J]. Redox Biol,2018,15:253-265.
    [9] McEvilly M,Popelas C,Tremmel B. Use of uridine triacetate for the management of fluorouracil overdose[J]. Am J Health Syst Pharm,2011,68(19):1806-1809.
    [10] Gallai V,Mazzotta G,Montesi S,et al. Effects of uridine in the treatment of diabetic neuropathy:an electrophysiological study[J]. Acta Neurol Scand,1992,86(1):3-7.
    [11] Mironova GD,Khrenov MO,Talanov EY,et al. The role of mitochondrial KATP channel in anti-inflammatory effects of uridine in endotoxemic mice[J]. Arch Biochem Biophys,2018,654:70-76.
    [12] Le TT,Ziemba A,Urasaki Y,et al. Disruption of uridine homeostasis links liver pyrimidine metabolism to lipid accumulation[J]. J Lipid Res,2013,54(4):1044-1057.
    [13] Sun Q. Glutamate excitotoxicity and the effect of glutamate-glutamine cycle in the cochlea (耳蜗谷氨酸兴奋性毒性及谷氨酸—谷氨酰胺循环机制的研究)[D]. Beijing:PLA Postgraduate Medical School,2004.
    [14] Fuhrman S,Palkovits M,Cassidy M,et al. The regional distribution of N-acetylaspartylglutamate (NAAG) and peptidase activity against NAAG in the rat nervous system[J]. J Neurochem,1994,62(1):275-281.
    [15] Zhao J,Ramadan E,Cappiello M,et al. NAAG inhibits KCl-induced[3H]-GABA release via mGluR3,cAMP,PKA and L-type calcium conductance[J]. Eur J Neurosci,2001,13(2):340-346.
    [16] Sanabria ER,Wozniak KM,Slusher BS,et al. GCP II (NAALADase) inhibition suppresses mossy fiber-CA3 synaptic neurotransmission by a presynaptic mechanism[J]. J Neurophysiol,2004,91(1):182-193.
    [17] Romei C,Raiteri M,Raiteri L. Glycine release is regulated by metabotropic glutamate receptors sensitive to mGluR2/3 ligands and activated by N-acetylaspartylglutamate (NAAG)[J]. Neuropharmacology,2013,66:311-316.
    [18] Fulop T,Radabaugh S,Smith C. Activity-dependent differential transmitter release in mouse adrenal chromaffin cells[J]. J Neurosci,2005,25(32):7324-7332.
  • 期刊类型引用(0)

    其他类型引用(1)

计量
  • 文章访问数:  180
  • HTML全文浏览量:  8
  • PDF下载量:  465
  • 被引次数: 1
出版历程
  • 收稿日期:  2021-04-06
  • 修回日期:  2021-09-13
  • 刊出日期:  2021-10-24

目录

    /

    返回文章
    返回
    x 关闭 永久关闭