抑郁症神经元自噬机制及中医药调节作用研究进展

Neuronal Autophagy in Depression and Regulatory Effect of Traditional Chinese Medicine:A Review

抑郁症是以情绪持续低落为主要特征的精神疾病,严重威胁人们的健康。近几年来神经元自噬作为应激反应的一个重要方面也被视为抑郁症发病机制假说而提出。相关研究综合表明,自噬不足或过度均会引起神经元损伤,抑郁症动物模型表现出神经元自噬激活或受抑两种状态,因此,神经元自噬可能是参与抑郁症发病的一把双刃剑。中医认为本病的发生与肝郁脾虚密切相关,而中药对抑郁症神经元自噬的调节也呈现出多种多样的方式,其中调节神经元自噬的中药单体均具有保护神经或穿透血脑屏障的功能,而中药复方从其功效来看,多属于疏肝或健脾类方剂,与抑郁症的核心病机肝郁和脾虚相契合。从中医药对抑郁症模型神经元自噬的综合调节作用来看,其治疗抑郁症可能是多靶点、多通路和多系统共同作用的结果。该文基于神经元自噬参与抑郁症的病理学和治疗的新证据对当前研究的局限性进行了讨论,以期为后期同类研究及中医药抗抑郁研究提供思路和借鉴。

Depression is a mental illness characterized by persistent negative feelings,which has seriously threatened people’s health. In recent years,neuronal autophagy,an important stress response,has also been regarded as a hypothesis for the pathogenesis of depression. Relevant studies have shown that either insufficient or excessive autophagy triggers neuronal damage,and activated or inhibited neuronal autophagy can be observed in animal models of depression. Therefore,neuronal autophagy may be a double-edged sword involved in the pathogenesis of depression. It is believed in traditional Chinese medicine(TCM)that the occurrence of this disease is closely related to liver depression and spleen deficiency. Chinese medicine regulates the neuronal autophagy via multiple ways. The TCM monomers that regulate neuron autophagy are capable of protecting nerves or penetrating the blood-brain barrier. TCM compounds designed for soothing liver or invigorating spleen have been proved effective against this disease,demonstrating that the core pathogenesis of depression lies in liver depression and spleen deficiency. The regulatory effects of TCM on neuronal autophagy in depression models might result from its action on multiple targets,multiple pathways,and multiple systems.This paper discussed the limitations in current research based on the involvement of neuronal autophagy in depression and its treatments,in order to provide ideas for later similar research and that concerning TCM treatment of depression.