神经药理学报

神经药理学报 ›› 2021, Vol. 11 ›› Issue (1): 11-17.DOI: 10.3969/j.issn.2095-1396.2021.01.002

• 研究论文 • 上一篇    下一篇

蛇床子素对催产素受体沉默大鼠皮质区神经递质及焦虑抑郁行为的影响

范旭坤，孙逸，宋双双，丛怡帆，侯雪芹   

  1. 山东第一医科大学（山东省医学科学院）药学院，泰安，271016，中国
  • 出版日期:2021-02-26 发布日期:2021-02-26
  • 通讯作者: 侯雪芹，女，医学博士，硕士生导师；研究方向：神经药理学；Email：xqhou@tsmc.edu.cn
  • 作者简介:范旭坤，女；研究方向：神经药理学；Email：463421841@qq.com
  • 基金资助:
    大学生创新创业课题项目（No.S202010439136），山东省重点研发项目（No.2019GSF108069），国家青年基金项目（No.81703901）

Effects of Osthole on Cortical Neurotransmitters and the Anxietyand Depresion-Like Behaviors in the Oxytocin Receptor-Silencing Rats#br#

FAN Xukun，SUN Yi，SONG Shuangshuang，CONG Yifan，HOU Xueqin#br#   

  1. Institution of Pharmacological，Shandong First Medical University & Shang dong Academy of Medical Sciences，Tai’an，271016，China
  • Online:2021-02-26 Published:2021-02-26
  • Contact: 侯雪芹，女，医学博士，硕士生导师；研究方向：神经药理学；Email：xqhou@tsmc.edu.cn
  • About author:范旭坤，女；研究方向：神经药理学；Email：463421841@qq.com
  • Supported by:
    大学生创新创业课题项目（No.S202010439136），山东省重点研发项目（No.2019GSF108069），国家青年基金项目（No.81703901）

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摘要：

目的： 探讨皮质区单胺类、氨基酸类和胆碱类神经递质与基底前脑催产素受体间相关性，阐明蛇床子素对催产素受体（oxytocin receptor，OTR）神经递质信号途径的作用及其对焦虑抑郁样行为的影响；方法：利用RNA干扰技术沉默大鼠基底前脑OTR，运用高架十字迷宫和强迫游泳实验观察蛇床子素对焦虑抑郁样行为的作用，运用Q-Orbitrap 高分辨液质联用检测大鼠脑皮质区神经递质含量变化；结果 在高架十字迷宫中，OTR沉默组大鼠进入开放臂次数、停留时间明显减少（P<0.05），蛇床子素（12.5mg·kg-1）干预后可增加大鼠进入开放臂次数和停留时间（P<0.01）。强迫游泳结果显示，与对照组相比，OTR沉默组大鼠不动时间延长（P<0.05），与OTR沉默组比，蛇床子素（12.5、25 mg·kg-1）能缩短不动时间（P<0.05）。OTR沉默组脑部皮质区的多巴胺（DA）和L-谷氨酸（L-GLU）比对照组水平高（P<0.05），5-羟色胺（5-HT）、γ-氨基丁酸（GABA）、乙酰胆碱（Ach）比对照组下降（P<0.05）；蛇床子素（12.5 mg·kg-1）可下调DA水平（P<0.05），上调5-HT、GABA和Ach水平（P<0.05）。蛇床子素（25 mg·kg-1）上调5-HT和Ach水平（P<0.05）；结论： 基底前脑OTR可能参与调控皮质神经递质，蛇床子素对基底前脑OTR沉默大鼠的焦虑抑郁行为有改善作用，其机制可能与基底前脑OTR-皮质神经递质之间的信号网络有关。

关键词: 焦虑抑郁, 基因沉默, 催产素受体, 神经递质, 蛇床子素

Abstract:

Objective: To explore the role of oxytocin receptor (OTR) in regulating anxiety- and depression-like behaviors and monoamine, amino acids and choline neurotransmitters in the cerebral cortex. And to investigate the effects of osthole on neurotransmitters in OTR silencing rats. Method: OTR silencing rats were established via short hairpin RNA (shRNA). Elevated plus maze and forced swimming test were used to observe the effect of osthole on anxiety- and depression-like behaviors. Q-orbitrap HPLC-HRMS was applied to detect neurotransmitters in the cerebral cortex of rats. Results: In the elevated plus maze, the number of entering the open arms and the residence time in the open arms were significantly reduced in the OTR-shRNA rats compared with the control group (P<0.05). Osthole (12.5 mg·kg-1) treatment increased the number of entering the open arms and the residence time in the open arms compared with the OTR-shRNA group (P<0.01). Forced swimming test showed that the OTR-shRNA group rats were immobile for longer than the control group (P<0.05). The immobile time in the osthole (12.5 mg·kg-1 and 25 mg·kg-1) groups were reduced than that in the OTR-shRNA group (P<0.05). Compared with the control group, the levels of dopamine (DA) and L-glutamic acid in the cerebral cortex of the OTR-shRNA group were higher (P<0.05), and the levels of 5-hydroxytryptamine (5-HT), gamma aminobutyric acid (GABA), and acetylcholine (Ach) were significantly lower (P<0.05). Osthole (12.5 mg·kg-1) reduced the level of DA, and increased the level of 5-HT, GABA and Ach (P<0.05), whereas osthole (25 mg·kg-1) increased the level of 5-HT and Ach (P<0.05). Conclusions: Osthole could influence neurotransmitters in the cerebral cortex, and attenuate anxiety- and depression-like behaviors, which may be through regulating the OTR pathway. It provides a new direction and basis for the research in central nervous system disorders, such as depression.

Key words: anxiety and depression, gene silencing, oxytocin receptor, neurotransmitters, osthole

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