河北医科大学学报 ›› 2025, Vol. 46 ›› Issue (5): 507-513.doi: 10.3969/j.issn.1007-3205.2025.05.003

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奥拉西坦对原代胎鼠皮层神经元的保护作用及机制研究

  

  1. 1.河北医科大学第二医院神经外科，河北 石家庄 050000；2.河北医科大学第二医院感染控制处，河北 石家庄 050000

  • 出版日期:2025-05-25 发布日期:2025-05-23
  • 作者简介:曹旭华(1985-)，男，河北深泽人，河北医科大学第二医院副主任医师，医学硕士，从事神经外科学疾病诊治研究。

  • 基金资助:
    河北省自然科学基金生物医药联合基金培育项目(H2020206640)

The protective effect and mechanism of oxiracetam on primary fetal rat cortical neurons

  1. 1.Department of Neurosurgery, the Second Hospital of Hebei Medical University, Shijiazhuang 
    050000, China; 2.Department of Hospital Infection Control, the Second Hospital of 
    Hebei Medical University, Shijiazhuang 050000, China

  • Online:2025-05-25 Published:2025-05-23

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摘要： 目的 探究奥拉西坦对原代胎鼠皮层神经元的保护作用及相关机制，分析奥拉西坦在N-甲基-D-天冬氨酸受体（N-methyl-D-aspartic acid receptor，NMDA受体）上作用的关键位点。
方法 通过原代胎鼠皮层神经元钙离子成像技术以及分子对接技术相结合，从细胞培养及分子水平两个方面阐述奥拉西坦对神经元的保护作用，分析其主要分子机制。
结果 原代胎鼠皮层神经元的细胞培养结果显示：奥拉西坦能够改善谷氨酸导致的神经毒性。不同浓度梯度的奥拉西坦孵育1 min可下调谷氨酸诱导的细胞内［Ca2+］i升高，并呈现剂量-效应反应现象。随着奥拉西坦浓度增至30 μmol/L，谷氨酸引起的钙浓度峰值显著下调至（78.45±3.12）%，AUC降至（77.06±1.39）%，再提高奥拉西坦浓度对于钙浓度峰值变化不十分明显。最终计算得到奥拉西坦对谷氨酸引发的细胞［Ca2+］i浓度峰值升高的半抑制浓度（half maximal inhibitory concentration，IC50）为15.34 μmol/L、曲线下面积（area under curve，AUC）的IC50为14.26  μmol/L。分析奥拉西坦与NMDA受体主要结合位点为ASN-599、LEU-601、PRO-602和GLN-604，结合能为-3.34 kcal/mol。
结论 奥拉西坦可以与谷氨酸受体有效结合，改善谷氨酸诱导的细胞内钙超载发挥神经保护作用。


关键词: 奥拉西坦, 神经元, 钙离子

Abstract: Objective To explore the protective effect and mechanism of oxiracetam on primary fetal rat cortical neurons and to analyze the key sites of oxiracetam acting on N-methyl-D-aspartic acid receptor (NMDA). 
Methods By using calcium ion imaging technology and molecular docking techniques on primary fetal rat cortical neurons, the protective effect of oxacetam on neurons were described at the cellular and molecular level and the molecular mechanism was analyzed. 
Results The results of cell culture of primary fetal rat cortical neurons showed that oxiracetam could ameliorate glutamate-induced neurotoxicity.Incubation with oxiracetam at varying concentration gradients for 1 min down-regulated glutamate-induced intracellular calcium ion (［Ca2+］i) elevation in a dose-response effect. As the concentration of oxiracetam increased to 30 μmol/L, the peak calcium concentration caused by glutamate was significantly reduced to (78.45±3.12)%, and the area under the curve (AUC) decreased to (77.06±1.39)%. Increasing the concentration of oxiracetam further did not result in significant changes in the peak calcium concentration.The final calculation showed that half maximal inhibitory concentration (IC50)of oxiracetam on peak increase in glutamate-induced ［Ca2+］i concentration was 15.34 μmol/L and that of AUC was 14.26 μmol/L, respectively. Oxiracetam binded to NMDA receptors at ASN-599, LEU-601, PRO-602, and GLN-604, with a binding energy of -3.34 kcal/mol. 
Conclusion Oxiracetam can effectively bind to glutamate receptors and play a neuroprotective role in improving glutamate-induced intracellular calcium overload.


Key words: oxiracetam, neurons, calciumion

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