基于血脑PK-PD和结构方程模型的银杏叶提取物多组分协同抗脑缺血作用研究

项目名称： 基于血脑PK-PD和结构方程模型的银杏叶提取物多组分协同抗脑缺血作用研究

项目编号： No.81503206

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： 郭莹

作者单位： 浙江中医药大学

项目金额： 18万元

中文摘要： 多组分协同作用是中药发挥整体药效的关键，但其协同作用机制有待探究。前期研究发现，多组分相互作用可影响体内动力学过程，推测体内过程改变是其协同作用机制之一。如何定量解析多组分体内行为和药效间的关系，是中药研究的难点之一。本项目拟从整体动物、细胞、分子层面，选择与脑缺血性损伤密切相关的药效指标，评价银杏叶提取物中黄酮和萜内酯抗脑缺血的协同作用；通过测定血和脑透析液中多组分PK、PD，由PK分析黄酮和萜内酯合用(EGB)对多组分体内过程（吸收、脑内分布）的影响；PK-PD采用结构方程模型定量解析，探索吸收入血和分布入脑的多组分与药效的因果关系，阐明EGB多组分协同保护脑缺血性损伤的作用机制。该项目采用血、脑多组分PK-PD、数学模型定量解析等方法，从药理作用、体内过程、多组分和药效的定量关系三方面，探讨多组分的协同作用，可为EGB原料药及制剂质量控制提供依据，也可为中药多组分研究提供思路。

中文关键词： 药动-药效；结构方程模型；银杏叶提取物；多组分协同作用；脑缺血

英文摘要： The synergetic effect of multi-components is the key of traditional Chinese medicine (TCM) to play the overall effect, but the mechanism is needed to be studied further. Our previous study shows that interactions among multi-components can have influence on pharmacokinetic process. So we suppose that changing pharmacokinetic process may be one of the mechanisms of their synergetic effect. How to resolve the complex relations between multi-components’ behavior in vivo and their synergetic effect quantitatively is one of the difficulties in TCM study. In this project, we will select pharmacological effects closely related to cerebral ischemic injury from such levels as whole animal, cell, molecule to evaluate the synergetic effect of ginkgo flavonoids and ginkgo terpene lactones in Ginkgo biloba extract (EGB) on cerebral ischemic injury. Determine pharmacokinetic (PK) and pharmacodynamic (PD) parameters both in blood and brain dialysate. Analyze the influence of ginkgo flavonoids combined with ginkgo terpene (EGB) on multi-components’ absorption and distribution to brain by PK parameters. Use structural equation model (SEM) to resolve causality of multi-components both in blood and brain and the effect quantitatively on basis of PK-PD. Illuminate the protective effect mechanism of multi-components’ synergetic effect in EGB on cerebral ischemic injury. In this project, mechanisms of multi-components’ synergetic effect will be explored from 3 aspects: pharmacological effects, pharmacokinetic process, quantitative relations between multi-components and pharmacological effects, using such methods as multi-components’ PK-PD both in blood and brain, quantitative analysis of mathematical model and etc. It can provide basis for quality control of EGB crude drugs and related preparations. It can also provide references for study of multi-components in TCM.

英文关键词： pharmacokinetics(PK)-pharmacodynamics(PD);structural equation model (SEM);Ginkgo biloba extract (EGB);multi-components’ synergetic effect;cerebral ischemia