“升降平调”加味温胆汤的情志双向调节作用机制研究

Nowadays，fast-paced work and lifestyle make people's psychological load increasing.Depression, anxiety and depressive anxiety have become the common diseases of today's society .At present, anti-anxiety and anti-depression drugs used in clinical have a variety of pharmacological effects,while they have the following shortcomings: slow onset, inadequate response, narrow safety range, many medical contraindications and other defects.Therefore, the effective emotional adjustment method and drugs of Chinese medicine have become the focus of attention.With the help of the Chinese sentiment theory, the preliminary work, and the latest research progress at home and abroad, we put forward the following hypothesis: Wendan Decoction,the Chinese herbal compound decoction with the adjustment function, may affect the neuronal synaptic plasticity of different brain regions by regulating 5-HT-mediated ERK / MAPK pathway, thus exerting two-way regulation of anti-intelligence effect.Applying the praxiology, morphology, molecular biology and other modern research techniques around the hypothesis and taking the plasticity of the emotional circuit as the starting point to investigate the effect of Jiawei Wendan Decoction on synaptic plasticity in different brain regions such as amygdala, hippocampal CA3 region, prefrontal cortex and hypothalamus and to elucidate the two-way regulation mechanism of the antidepressant and anxious emotions of Jiawei Wendan Decoction.Thus it is expected that providing a new scientific basis for the effective clinical application of Jiawei Wendan Decoction.

当今社会高效率快节奏的工作、生活方式，致使人们的心理负荷不断加重，抑郁症、焦虑症以及抑郁焦虑共病已经成为当今社会的多发病、常见病。目前临床上使用多种药理学作用不同的抗焦虑、抑郁药物，具有起效缓慢、反应不充分、安全范围窄、用药禁忌较多等缺陷，因此从中医药中寻求有效的情志病证防治新思路成为关注的焦点。本项目在中医情志理论指导下，在前期工作基础上，结合国内外最新研究进展，提出工作假说：升降平调的中药复方加味温胆汤可能通过调节5-HT介导的ERK/MAPK通路，影响情绪回路的不同脑区神经元突触的可塑性，从而发挥抗情志双向调节作用。围绕假说综合应用行为学、形态学及分子生物学等现代研究技术，以情绪回路的可塑性为切入点，探讨加味温胆汤对杏仁核、海马CA3区、前额皮质和下丘脑等不同脑区的突触可塑性的影响，阐明加味温胆汤抗抑郁、焦虑的情志双向调节作用机制，以期为加味温胆汤有效临床实提供新的科学依据。

抑郁症和焦虑症是两种发病机制密切关联的精神类疾病，即可以单独发病亦可以同时出现，其病因和病理生理学机制复杂，至今尚未完全阐明，神经递质假说并不能完全解释抑郁症、焦虑症的发病机制以及起效缓慢、疗效不确切等临床实际问题，因此探讨抑郁症、焦虑症的发病的关键环节，寻求新的临床药物治疗靶点是目前亟待解决的问题。中医药因擅长身心整体论治而在疾病的防治中具有一定的优势，中药复方以多成分、多环节、多层次、多靶点的药理学作用见长。因此，本项目在中医情志理论指导下，在前期工作基础上，结合国内外最新研究进展，提出工作假说：升降平调的中药复方加味温胆汤可能通过调节5-HT介导的ERK/MAPK通路，影响情绪回路的不同脑区神经元突触的可塑性，从而发挥抗情志双向调节作用。研究结果表明，加味温胆汤能够改善抑郁、焦虑行为学表现；抑郁、焦虑模型大鼠情绪加工神经环路5-HT含量以及5-HT1A、Ras、Raf、MEK、ERK蛋白、基因表达并不一致，加味温胆汤干预作用也有差异。前额皮质和海马区可能是抑郁、焦虑症发病主要相关脑区，加味温胆汤情志双向调节作用可能与前额皮质、海马 5-HT 含量、5-HT1A蛋白表达有关，其抗抑郁作用优于抗焦虑作用。