中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (1): 178-184.doi: 10.4103/1673-5374.314321

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

瓜子金皂苷己可保护海马神经元免受谷氨酸诱导的细胞毒性

  

  • 出版日期:2022-01-05 发布日期:2021-09-22

Polygalasaponin F protects hippocampal neurons against glutamate-induced cytotoxicity

Chong Sun1, Xin-Cheng Cao1, Zhi-Yang Liu1, Chao-Lin Ma1, Bao-Ming Li1, 2, *   

  1. 1Laboratory of Cognitive Function and Disorder, Institute of Life Science, Nanchang University, Nanchang, Jiangxi Province, China; 2Institute of Brain Science and Department of Psychology, School of Education, Hangzhou Normal University, Hangzhou, Zhejiang Province, China
  • Online:2022-01-05 Published:2021-09-22
  • Contact: Bao-Ming Li, PhD, bmli@ncu.edu.cn or bmli@hznu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 31971035 (to BML), 31771182 (to BML), 81471116 (to BML); and the Natural Science Foundation of Jiangxi Province of China, Nos. 20171BAB204019 (to CS), 20192ACB20022 (to CS).

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摘要：

胞外高浓度谷氨酸具有巨大的神经元兴奋性毒性，可通过对N-甲基-D-天冬氨酸受体的过度激活导致神经元死亡。神经元兴奋性毒性也被认为与多种急性或慢性神经系统疾病（如卒中和阿尔茨海默病）密切相关。瓜子金皂苷己是从中药远志分离出的一种三萜皂苷单体，既往研究表明具有神经保护作用，但其作用机制并不清楚。为探索瓜子金皂苷己的神经保护作用机制，实验将经瓜子金皂苷己预处理的海马神经元暴露于谷氨酸24h，发现瓜子金皂苷己可以浓度依赖性方式抑制谷氨酸诱导的海马神经元的死亡，同时抑制谷氨酸诱导的神经元钙超载，并部分抑制了N-甲基-D-天冬氨酸受体介导的跨膜电流，阻止谷氨酸诱导的N-甲基-D-天冬氨酸受体亚基NR2A表达下调和NR2B表达上调，同时还能上调磷酸化CREB和脑源性神经营养因子的表达。可见瓜子金皂苷己调节N-甲基-D-天冬氨酸受体的作用产生了保护海马神经元免受谷氨酸诱导细胞毒性的效应。实验于2017年12月29日经南昌大学动物伦理委员会批准（批准号2017-0006）。

https://orcid.org/0000-0001-8135-7375 (Bao-Ming Li)

关键词: 瓜子金皂苷己, 谷氨酸兴奋毒性, Ca2+稳态, N-甲基-D-天冬氨酸受体, 海马神经元, 神经保护, 磷酸化环磷腺苷效应元件结合蛋白, 脑源性神经营养因子

Abstract: Excess extracellular glutamate leads to excitotoxicity, which induces neuronal death through the overactivation of N-methyl-D-aspartate receptors (NMDARs). Excitotoxicity is thought to be closely related to various acute and chronic neurological disorders, such as stroke and Alzheimer’s disease. Polygalasaponin F (PGSF) is a triterpenoid saponin monomer that can be isolated from Polygala japonica, and has been reported to protect cells against apoptosis. To investigate the mechanisms underlying the neuroprotective effects of PGSF against glutamate-induced cytotoxicity, PGSF-pretreated hippocampal neurons were exposed to glutamate for 24 hours. The results demonstrated that PGSF inhibited glutamate-induced hippocampal neuron death in a concentration-dependent manner and reduced glutamate-induced Ca2+ overload in the cultured neurons. In addition, PGSF partially blocked the excess activity of NMDARs, inhibited both the downregulation of NMDAR subunit NR2A expression and the upregulation of NMDAR subunit NR2B expression, and upregulated the expression of phosphorylated cyclic adenosine monophosphate-responsive element-binding protein and brain-derived neurotrophic factor. These findings suggest that PGSF protects cultured hippocampal neurons against glutamate-induced cytotoxicity by regulating NMDARs. The study was approved by the Institutional Animal Care Committee of Nanchang University (approval No. 2017-0006) on December 29, 2017.

Key words: BDNF, Ca2+ homeostasis, excitotoxicity, glutamate, hippocampal neurons, pCREB, polygalasaponin F, neuroprotection, NR2A, NR2B