整合动态PK-PD相关性分析在中药药效物质基础发现中的研究策略  

Integrative dynamic PK-PD correlation analysis and its application in discovery of pharmacodynamic material basis of traditional Chinese medicine

作　　者：王玉昆 王鹏 王威宇[1,2] 秦雪梅 高晓霞[1,2,3] WANG Yukun;WANG Peng;WANG Weiyu;QIN Xuemei;GAO Xiaoxia(Modern Research Center for Traditional Chinese Medicine,Shanxi University,Taiyuan 030006,China;The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education,Shanxi University,Taiyuan 030006,China;The Key Laboratory of Effective Substances Research and Utilization in Traditional Chinese Medicine of Shanxi Province,Taiyuan 030006,China;Southern Medical University,Guangzhou 510515,China)

机构地区：[1]山西大学中医药现代研究中心,山西太原030006 [2]山西大学化学生物学与分子工程教育部重点实验室,山西太原030006 [3]地产中药功效物质研究与利用山西省重点实验室,山西太原030006 [4]南方医科大学,广东广州510515

出　　处：《药物评价研究》2023年第6期1157-1167,共11页Drug Evaluation Research

基　　金：国家自然科学基金资助项目(32174099,31473415,81001688);山西省基础应用项目面上项目(20210302123432);名优晋药再开发山西省重点实验室项目(202104010910001);地产中药功效物质研究与利用山西省重点实验室项目(202105D121009)。

摘　　要：中药药效物质基础研究是解释中医药作用机制的基石,然而中药复方作为一个复杂体系,作用机制与体内效应过程不明确等问题长期桎梏中医药事业的发展。药动学-药效学(PK-PD)相关性研究是动态表征和定量描述活性成分与药理作用之间相关性的有效方法,将时间、浓度和效应结合起来,已经成为阐明中药药效物质基础的技术策略,但是目前研究大都集中在结构明确的化学药物,缺乏符合中医药发展模式的相关策略。因此,非常有必要深入挖掘新的研究策略,建立符合中医药特色的PK-PD模型,通过进行方法开发与技术重组,利用从化学物质基础、关键成分的筛选、整合PK-PD相关性的多维整合的研究思路,引入代谢组学等现代技术手段,全方位、及时灵敏地表征药效特点,评价药动学考察药物机制研究,旨在构建更易于发现药效物质的技术体系,为阐明中药复方的药效物质基础提供参考。The research on the material basis of medicinal effect of traditional Chinese medicine(TCM)is the cornerstone of explaining the mechanism of action of TCM.However,as a complex system,the development of TCM has long been hindered by the unclear mechanism and effect process in vivo.Pharmacokinetic-pharmacodynamic(PK-PD)correlation study is an effective method to dynamically characterize and quantitatively describe the correlation between active ingredients and pharmacological actions.The combination of time,concentration and effect has become a technical strategy to clarify the material basis of the efficacy of TCM.However,most of the current research focuses on chemical drugs with clear chemical composition,and lacks relevant strategies in line with the development model of TCM.Therefore,it is very necessary to deeply explore new research strategies,establish a PK-PD model that conforms to the characteristics of TCM,conduct method development and technical reorganization,use multi-dimensional integration research ideas from the basis of chemical substances,the screening of key components,and the integration of PK-PD correlation,introduce modern technical means derived from metabonomics,and comprehensively and sensitively demonstrate the evaluation of pharmacodynamic characteristics,and pharmacodynamic study of drug mechanisms.The aim is to build a technical system that is easier to find effective substances,and to provide a reference for clarifying the material basis of the efficacy of TCM prescriptions.

关 键 词：药动学 药效学 药动学-药效学相关 血清药物化学 代谢组学 中药 药效物质 

分 类 号：R914.2[医药卫生—药物化学] R284.1[医药卫生—药学]