项目名称： 基于“血清药物化学-药代动力学-代谢组学”的体外培育牛黄活性成分辨识与机制研究

项目编号： No.81503225

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李喜平

作者单位： 华中科技大学

项目金额： 18万元

中文摘要： 阐明中药药效物质基础和作用机制始终是其研究开发过程中的困惑和难点。体外培育牛黄为国家药典收载的名贵中药，尽管当前普遍认为其药效与其主要成分胆汁酸有关，但仍缺乏强有力证据支持。课题组前期研究发现CBS可有效治疗胆汁淤积症（IC），本项目将在此基础之上，基于“血清药物化学-药代动力学-代谢组学”三维整合体系研究思路，通过分析CBS化学组多维特征指纹图谱和体内血中移行成分，初步鉴定体内直接作用物质，并进一步考察入血胆汁酸药代动力学及其相互作用；通过分析CBS整体和单个化学成分分别干预动物模型前后肝组织、血清及尿液内源性物质变化规律，筛选与药效相关的生物标记物，构建CBS干预后效应物质-病症（IC症）桥连代谢网络，综合所有研究结果，有望阐明CBS的药效物质基础及治疗IC的多组分、多途径、多靶点的整体作用机制。

中文关键词： 体外培育牛黄；中药血清药物化学；药代动力学；代谢组学；药效物质基础

英文摘要： Revealing the material foundation and mechanism of Chinese medicine is a confusing and difficult task in research and development. Calculus Bovis Sativus (CBS) is one kind of rare Traditional Chinese Medicine (TCM) recorded in state Pharmacopoeia, although people generally believe its pharmacological activities correlate with its major ingredients, the evidence is still untenable and insufficient. Previously we confirmed the potent capacity of CBS to treat intrahepatic cholestasis (IC), based on this work, the integrated three-dimensional “serum pharmacochemistry - pharmacokinetics - metabolomics system is established hereon. By comparing multi-dimensional fingerprints with spectrum collected from analyzing the transitional compositions into the blood, the absorbed bioactive components could be preliminary identified in mice serum after oral administration of CBS. Furthermore, the pharmacokinetic profiles of absorbed bioactive components are evaluated to understand their internal dynamic process and their potential interactions. Finally, by analyzing the effects of CBS or its single component on the metabolites profiling in serum, urine and liver tissues, metabolomics are employed to discriminate efficacy-correlated biomarkers and construct the molecular network linking efficacy components with disease model (IC). Bringing above results together, we could really understand the material basis which component truly works in CBS and verify whether CBS plays its mechanism by restoring the perturbed metabolic pathways in disease model in a manner of multi-components, multi-channels, multi-targets.

英文关键词： calculus bovis sativus;serum pharmacochemistry of traditional Chinese medicine;pharmacokinetics;metabolomics;pharma-material basis