如何选择和确定反映中药整合作用特点的药效指标，并用于开展多组分、多靶点效应的PK-PD结合研究，是中药PK-PD结合研究的重点和难点。本课题针对该研究中的药效指标筛选存在的主要关键问题，以生脉注射液为研究对象，首先采用血清蛋白质组学技术从血清低丰度蛋白中寻找与生脉抗心肌缺血作用相关，体现中药整合作用的血清生物标志物为候选药效指标。然后进一步通过体内药效-时间关系以及量-效关系考察，从候选药效指标中筛选出能够灵敏反映生脉体内浓度变化的药效指标，并建立定量分析方法，据此开展生脉多靶点效应药效动力学研究。同时，以生脉主要药效成分为药代标记物，开展多组分的药代动力学研究。最后，综合药代及药效动力学结果拟合建立生脉多组分、多靶点效应的PK-PD结合模型，揭示生脉抗心肌缺血的药效物质基础。本课题拟为中药PK-PD结合研究中的药效指标筛选探索一条新的途径并为中药PK-PD结合研究提供新的思路和方法参考。

It is important and difficult that how to select and confirm effect indices reflecting integral action of traditional Chinese medicines (TCM) and with which to study the integrated pharmacokinetics-pharmacodynamics (PK-PD) with multiple-components and multiple-targets effect of TCM. This project focuses on the main key question for selecting effect indices in the integrated PK-PD study of TCM. Using Shengmai injection (SMI) as research object, the technology of serum proteomics will be first applied to search biomarkers from serum low abundance protein as candidate effect indices, which are related with SMI’s protection on myocardial ischemia and reflect integral action of TCM. Then, candidate effect indices will be further selected through in vivo effect-time and doses-effect relationship investigation for determining the potential effect indices which can reflect sensitively drug concentration change of SMI in vivo. Quantitative analysis method will also be established for the confirmed effect indices and with which the multiple-targets effect pharmacodynamics study of SMI’s protection on myocardial ischemia will be carried out. Meanwhile, multiple-components pharmacokinetics study of SMI’s protection on myocardial ischemia will be performed using multiple effective components as pharmacokinetics markers. Finally, the integrated PK-PD models of SMI with multiple-components and multiple-targets effect will be established combining the pharmacokinetics and pharmacodynamics results. It might help to reveal effect material basis of SMI’s protection on myocardial ischemia through the integrated PK-PD models analysis. This project would attempt to explore a new path for the selection of effect indices and apply the new thread and method reference in the integrated PK-PD study of TCM.