中文摘要
疏肝解郁是中医治疗肝气郁结证的基本原则,其代表方剂柴胡疏肝散临床治疗肝气瘀滞证效果显著,但其疏肝作用的现代医学内涵不明。诸多学者围绕中枢单氨神经递质假说、神经营养因子假说和MARKs信号通路等对其进行了大量卓有成效的研究,另有学者则对通过外周调节糖皮质激素(GC)水平-恢复HPA轴功能-中枢结构功能恢复而治疗抑郁症进行了饶有兴趣的探索。现有研究表明柴胡疏肝散对抑郁模型大鼠体内皮质酮的含量有调控作用。本课题组前期通过代谢组学法研究证实外周GC水平的调节与抑郁症关系密切,抑郁症的转归与人体内GC代谢和神经递质的含量密切相关。本项目拟在前期研究基础上,以柴胡疏肝散为研究对象,通过代谢组学研究方法揭示在柴胡疏肝散的干预下,肝气郁结动物模型和临床患者体液中GC代谢谱的变化,以GC和神经递质浓度、代谢酶、转运体等多种机制相互补充与验证,为阐明柴胡疏肝散的作用机制和“疏肝”现代医学内涵提供依据和新思路。
英文摘要
The "Relieving the Depressed Liver" law is the basic principle to relieve the liver qi stagnation types depression from the point of view of Traditional Chinese Medicine(TCM) theory, literature and clinical practice.Chaihu-Shugan-San (CHSGS), a typical prescription,shows the significant clinical effect to reduce depression, based on soothing the liver and regulating mind. However, the modern medical connotation of CHSGS in the treatment of patients with depression is unclear. Many scholars have conducted much fruitful research around the monoamine neurotransmitter hypothesis,neurotrophic factor hypothesis and MAPKs signaling pathways. Otherwise, other scholars have been interesting to investigate treatment of depression through modulating the outer periphery of Glucocorticoid (GC) level - function recovery of HPA axis and structure and function of the central nervous system. The current research have shown that CHSGS effectively relieve depression by regulating corticosterone level in CUMS rat models. Besides, the previous metabolomic studies of the applicant have shown that the closely correlation between GC level and the clinical development of depresssion. As well as, the improvement of depression closely relates to outer glucocorticoids metabolism and neurotransmitters levels.In the proposed study,we intend to further reveal the changes of the GC metabolic profiling in the liver qi stagnation types depression animal models and depression patients in clinical before and after CHSGS treatment by GC metabolomics on the basis of preliminary studies. Various mechanisms such as GC metabolic profile, neurotransmitters concentration, metabolic enzymes and transporters will be complemented and verified. It will provide the solid foundation and new ideas to clarify the mechanism of CHSGS and modern medical connotation of "Relieving the Depressed Live" law.
