中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (2): 302-310.doi: 10.4103/1673-5374.265555

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

基于同位素标记相对和绝对定量分析中药抗抑郁作用的蛋白靶点

  

  • 出版日期:2020-02-15 发布日期:2020-05-25
  • 基金资助:

    中国国家自然科学基金项目(81573876)

Identification of protein targets for the antidepressant effects of Kai-Xin-San in Chinese medicine using isobaric tags for relative and absolute quantitation

Xian-Zhe Dong1, 2, Dong-Xiao Wang1, Tian-Yi Zhang1, Xu Liu1, Ping Liu1, Yuan Hu1   

  1. 1 Department of Clinical Pharmacology and Pharmacy, Center of Pharmacy, Chinese PLA General Hospital, Beijing, China
    2 Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing, China
  • Online:2020-02-15 Published:2020-05-25
  • Contact: Yuan Hu, PhD,huyuan1980619@126.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81573876 (to YH).

摘要:

开心散是一种由由人参、远志、茯苓和石菖蒲按3:3:2:2制备传统复方中药制剂,在中国被用于治疗情绪方面的疾病,但对其治疗机制中关键蛋白尚不可知。此次实验通过28d以不同应激方法建立慢性不可预知温和刺激抑郁大鼠模型,在在应激刺激14d后每天灌胃600mg/kg开心散。以蔗糖偏好测试检测大鼠抑郁样行为,以同位素标记相对和绝对定量蛋白组学分析海马组织中蛋白的变化。结果发现,开心散治疗2周能显著改善慢性不可预知温和刺激抑郁模型大鼠的抑郁样行为,且海马组织中有7种蛋白表达下调,26种蛋白表达上调。经蛋白组学功能分析见,这些蛋白可参与突触可塑性、神经发育和神经发生。实验结果显示,中药开心散对神经突触信号网络中关键节点蛋白有重要调控作用,这有助于了解中药开心散抗抑郁作用的机制,为其临床应用提供客观的理论支持。

orcid: 0000-0002-5348-1974 (Yuan Hu)

关键词: 同位素标记相对和绝对定量, 蛋白组学分析, 开心散, 神经发生, 突触可塑性, 蛋白网络, 抑郁中药, 脑源性神经营养因信号通路, 神经再生

Abstract: Kai-Xin-San consists of Ginseng Radix, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria at a ratio of 3:3:2:2. Kai-Xin-San has been widely used for the treatment of emotional disorders in China. However, no studies have identified the key proteins implicated in response to Kai-Xin-San treatment. In this study, rat models of chronic mild stress were established using different stress methods over 28 days. After 14 days of stress stimulation, rats received daily intragastric administrations of 600 mg/kg Kai-Xin-San. The sucrose preference test was used to determine depression-like behavior in rats, while isobaric tags were used for relative and absolute quantitation-based proteomics to identify altered proteins following Kai-Xin-San treatment. Kai-Xin-San treatment for 2 weeks noticeably improved depression-like behaviors in rats with chronic mild stress. We identified 33 differentially expressed proteins: 7 were upregulated and 26 were downregulated. Functional analysis showed that these differentially expressed proteins participate in synaptic plasticity, neurodevelopment, and neurogenesis. Our results indicate that Kai-Xin-San has an important role in regulating the key node proteins in the synaptic signaling network, and are helpful to better understand the mechanism of the antidepressive effects of Kai-Xin-San and to provide objective theoretical support for its clinical application. The study was approved by the Ethics Committee for Animal Research from the Chinese PLA General Hospital (approval No. X5-2016-07) on March 5, 2016.

Key words: brain-derived neurotrophic factor signal pathway, depression, isobaric tags for relative and absolute quantitation, Kai-Xin-San, neurogenesis, protein network, proteomics analysis, synaptic plasticity, traditional Chinese medicine