基于代谢网络“时-空”动态调控的当归四逆汤“温经通脉”作用配伍机制及其药效物质基础研究

The syndrome of cold coagulation and blood stasis is one of the common traditional Chinese medicine (TCM) syndromes in clinic, which often treated by the strategy of "warm menstruation and promote pulse" effectively. Danggui-Sini-Decoction (DSD）is a representative formula widely accepted by physicians accounting for its effect of "warming the meridians to dispel cold and nourishing blood to promote blood circulation". Though the prescription of DSD is exquisite, and its effect is confirmed, the compatible mechanism of prescription and bioactive components of DSD had not yet been elucidated. Therefore, the approach of "metabolic network "temporal-spatial" dynamic regulation" is proposed basing on the combination of technologies and methods including pharmaceutical analysis, pharmacology, and mathematical statistics. The metabolomic approach is utilized to characterize the potential biomarker in different compatibility of prescription at different time points in the pathological development of cold coagulation and blood stasis syndrome, the potential metabolic network will be revealed and the dynamic regulation mode of DSD in different compatibility will be described, meanwhile, the chemical constituents in different compatibility will be profiled by the method of liquid chromatography tandem with mass spectrometry, the relevant components relating to biomarkers will be screened by multivariate statistical correlation analysis, and the dynamic action mode of different constituents in different compatibility will be characterized. Based on this study, the compatibility mechanism of DSD related to "warm menstruation and promote pulse" effect will be elucidated, the effective basis will be clarified, and the scientific connotation and potential application of TCM formula will be further explored.

寒凝血瘀证是临床常见的中医证型之一，临床证治中常采用“温经通脉”治法，当归四逆汤为后世医家所公认的温经散寒、养血通脉代表方。虽然当归四逆汤组方精妙、疗效肯定，然而，在发挥“温经通脉”作用的过程中其组方配伍机制及药效物质基础仍未得以深入阐明；基于此，本课题提出基于代谢网络“时-空”动态调控的研究思路，综合药物分析、药理学、数理统计等多学科的技术和方法，一方面，运用代谢组学技术寻找当归四逆汤作用于寒凝血瘀证病变过程中不同时间点各配伍组方的起效生物标志物，推测其可能调控的代谢网络，描述配伍各部分起效的动态调控模式；另一方面，对不同配伍组成的化学成分进行液质联用表征，运用多元统计相关分析筛选与起效标志物变化相关性较强的化学成分，刻画配伍组成中各药效成分参与网络动态调控的作用模式。通过研究，深入揭示当归四逆汤发挥“温经通脉”作用的配伍机制，阐明其药效物质基础，进一步发掘中药复方的科学内涵和应用潜力。

寒凝血瘀证是临床常见的中医证型之一，临床证治中常采用“温经通脉”治法，当归四逆汤为后世医家所公认的温经散寒、养血通脉代表方。虽然当归四逆汤组方精妙、疗效肯定，然而，在发挥“温经通脉”作用的过程中其组方配伍机制及药效物质基础仍未得以深入阐明；基于此，本课题以当归四逆汤为研究对象，以代谢组学技术为核心，结合药物分析、药理学、数理统计、分子生物学等学科的技术和方法，运用代谢网络"时-空"动态调控的研究思路，对当归四逆汤的“温经通脉”作用治疗寒凝血瘀证的配伍规律及药效成分群进行研究。在本项研究中，一方面，课题组运用代谢组学技术锁定了当归四逆汤作用于寒凝血瘀证病变过程中不同时间点各配伍组方的起效生物标志物，推测其可能调控的代谢网络，描述配伍各部分起效的动态调控模式；另一方面，对不同配伍组成的化学成分进行液质联用表征，运用多元统计分析进行筛选，初步筛选出20个与药效相关的潜在活性成分。通过研究，深入揭示当归四逆汤发挥“温经通脉”作用的配伍机制，阐明其药效物质基础，进一步发掘中药复方的科学内涵和应用潜力。