中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (5): 837-845.doi: 10.4103/1673-5374.232478

• 原著:退行性病与再生 • 上一篇    下一篇

复方中药柴胡疏肝散抗抑郁效应的机制：下调miR-124表达解决对MAPK14和Gria3信号通路的抑制

  

  • 收稿日期:2018-04-19 出版日期:2018-05-15 发布日期:2018-05-15

Chaihu-Shugan-San exerts an antidepressive effect by downregulating miR-124 and releasing inhibition of the MAPK14 and Gria3 signaling pathways

Qiong Liu1, Ning-Ning Sun2, Zheng-Zhi Wu2, Da-Hua Fan3, 4, Mei-Qun Cao2   

  1. 1 Department of Cardiovascular Medicine, XiangYa Hospital of Central South University, Changsha, Hunan Province, China
    2 Shenzhen Institute of Geriatrics, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen,Guangdong Province, China
    3 The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong Province, China
    4 Chinese and Wsetern Integrative Medicine, Shcool of Medicine, Jinan University, Guangzhou, Guangdong Province, China.
  • Received:2018-04-19 Online:2018-05-15 Published:2018-05-15
  • Contact: Mei-Qun Cao, Ph.D. or Da-Hua Fan, Ph.D.,mqcao111@163.com or fan_dahua@163.com.
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 81503415, 81574038, 81603671; the China Postdoctoral Science Foundation Grant, No. 2016M600709; a grant from the Science and Technology Planning Project of Guangdong Province of China, No. 2014A020221062; a grant from the Science and Technology Planning Project of Shenzhen City of China, No.JCYJ20150401170235349, JCYJ20160428105749954.

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摘要：

有研究报道脑内mir-124表达异常与抑郁症的病理机制及治疗相关，中药柴胡疏肝散是中国传统医学的抗抑郁经典方剂，临床具有较好的抗抑郁作用，但作用机制尚不十分清楚。为此，实验采用孤养并进行28 d不可预见的慢性应激刺激构建慢性应激性抑郁模型大鼠，采用柴胡疏肝散2.835 mL/kg/d灌胃4周，每日1次。以实时定量PCR、miRNA芯片、western Blot 及透射电镜检测发现，柴胡疏肝散下调了抑郁模型大鼠海马内miR124的表达，提高了促神经元突触兴奋因子MAPK14和Gria3 mRNA和蛋白的表达，促进了海马神经元突触的形成。以旷场实验、糖水消耗实验和强迫游泳实验评价模型大鼠抑郁样行为改变发现，柴胡疏肝散灌胃后，抑郁模型大鼠的糖水消耗能力显著提高，在旷场实验和强迫游泳实验的抑郁样行为显著减少。上述数据证明，柴胡疏肝散通过下调mir-124表达，解除对MAPK14和Gria3通路的抑制，从而发挥了抗抑郁效应。

orcid:0000-0001-6981-975X(Mei-Qun Cao)
        0000-0003-4842-3742(Da-Hua Fan)

关键词: 中药, 柴胡疏肝散, 抑郁, 旷场试验, 蔗糖消耗试验, 强迫游泳试验, miR-124, 神经可塑性, MAPK14, Gria3, 神经再生

Abstract:

Dysregulation of miR-124 has been reported to be involved in the pathophysiology of depression. Chaihu-Shugan-San, a traditional Chinese medicine, has antidepressive activity; however, the underlying mechanisms remain unclear. In this study, to generate a rodent model of depression, rats were subjected to a combination of solitary confinement and chronic unpredictable mild stress for 28 days. Rats were intragastrically administered Chaihu-Shugan-San (2.835 mL/kg/d) for 4 weeks, once a day. Real-time reverse-transcription quantitative polymerase chain reaction, miRNA microarray, western blot assay and transmission electron microscopy demonstrated that Chaihu-Shugan-San downregulated miR-124 expression and upregulated the mRNA and protein levels of mitogen-activated protein kinase 14 (MAPK14) and glutamate receptor subunit 3 (Gria3). Chaihu-Shugan-San also promoted synapse formation in the hippocampus. The open field test, sucrose consumption test and forced swimming test were used to assess depression-like behavior. After intragastric administration of Chaihu-Shugan-San, sucrose consumption increased, while the depressive behaviors were substantially reduced. Together,these findings suggest that Chaihu-Shugan-San exerts an antidepressant-like effect by downregulating miR-124 expression and by releasing the inhibition of the MAPK14 and Gria3 signaling pathways

Key words: nerve regeneration, traditional Chinese medicine, Chaihu-Shugan-San, depression, open-field test, sucrose consumption test, forced swimming test, miR-124, neural plasticity, MAPK14, Gria3, neural regeneration