基于动态“失和/求和”网络的参麦方组分配伍优化研究

‘How to build a comprehensive evaluation index describing the dynamic change of the efficacy of traditional Chinese medicine (TCM)’ is a key scientific problem of compatibility optimization using QCAR-based approach. In the previous study, the applicant introduced TCM network pharmacology into compatibility optimization design and achieved promising results by setting biomolecular network as a optimization indicator. In this study, based on these progress, dynamic network of coronary heart disease with Qi-deficiency and blood-stasis (CHD-QB) rats will be developed using RNA-seq data of CHD-QB rats after oral administration of different combination of three active components form Shenmai formula. The similarity between dynamic networks will be calculated by integration of node status changes, node connection change as well as the impact of downstream regulatory, and therefore be set as the evaluation index for compatibility optimization of active components from Shenmai formula. This study is expected to develop a dynamic network –based strategy for compatibility optimization of active components, and will surely be help to enrich and expand the TCM network pharmacology discipline.

“如何构建符合中医药特点的药效综合评价指标，准确描述出机体状态的动态变化”是采用组效关系（QCAR）进行组分配伍优化设计的关键科学问题。在前期研究中，申请人将网络药理学引入中药组分配伍优化设计研究，从以中医整体观出发，将机体复杂的生物分子静态网络作为药效综合评价指标，取得了初步成效。本申请拟在此基础上，聚焦“定量描述机体生物分子网络动态变化”，以参麦方中三种有效组分为具体对象，采用RNA-seq等测序技术测定正常大鼠、模型大鼠和不同配伍比例样品给药后的转录组学变化，研究构建冠心病动态“失和/求和”网络模型；进而将网络节点状态变化、节点连接强弱变化、节点对下游调控力度变化等纳入评价体系，利用动态网络变化的相似程度来定量评价中药对失和网络的整合调节作用，据此进行参麦方有效组分的配伍比例优化设计，探索建立中药组分配伍网络整体优化策略。

项目背景：“如何构建符合中医药特点的药效综合评价指标，准确描述出机体状态的动态变化”是采用组效关系进行组分配伍优化设计的关键科学问题。在前期研究中，课题组将网络药理学引入中药组分配伍优化设计研究，从以中医整体观出发，将机体生物静态网络作为药效综合评价指标，取得了初步成效。.主要研究内容及结果：本项目在此基础上，本研究以参麦方中三种有效组分（人参二醇型皂苷、人参三醇型皂苷和麦冬皂苷）为具体对象，测定正常、疾病模型和不同配伍比例样品给药后心衰动物模型的转录组数据，构建 “失和/求和”网络模型；进而将网络节点状态变化、节点连接强弱变化、节点对下游调控力度变化等纳入评价体系，采用动态网络稳定性来定量评价中药对失和网络的整合调节作用，据此进行参麦方有效组分的配伍比例优化设计并对优化结果进行了实验验证。.科学意义：本研究不仅丰富和拓展了中药网络药理学研究的技术方法，还证实了从整体网络动态结构角度评价中药整体药效的可行性，为中药组分配伍优化提供了新策略。