血脑屏障(BBB)上的转运蛋白对药物进入脑部发挥药效起到重要的作用。中药防治阿尔茨海默病(AD)研究尚未考虑到BBB上的转运蛋白，药效评价缺乏系统性，迫切需要构建更加科学的药效评价体系。本课题拟以知母和丹参为模型药材，围绕BBB转运蛋白P-gp和BCRP，采用脑微血管内皮细胞模型和转基因小鼠模型，研究知母和丹参活性成分对P-gp和BCRP的调控；进而应用AD动物模型，研究在生理、AD病理损伤以及药物作用下中药活性成分与P-gp和BCRP的相互关系，揭示其透过BBB以作用于AD病理靶点的转运机制；同时研究病理损伤和药物干预对P-gp和BCRP转运蛋白表达的影响，以及脑部内源性神经递质的变化；从外源性中药活性成分、内源性物质变化和转运蛋白自身表达三个层面，构建基于血脑屏障转运蛋白的中药防治AD的药物效应定量评价体系，促进治疗AD的中药新药研发，并且能为中药与西药合并用药治疗AD提供科学依据。

Drug transporters on Blood-brain barrier(BBB) play an important role in delivering drugs into the brain to exert effects. However,drug transporters are not considered in the treatment of Alzheimer’s disease(AD) using traditional Chinese medicines(TCM).This project is focused on the development of quantitative evaluation system for TCM effects on AD based on drug transporters P-gp and BCRP on BBB. Zhimu and Danshen are selected as model herbs and the modulation effects of active components in each herb on the transporters P-gp and BCRP are to be investigated,using BMEC cell model and P-gp or BCRP knockout mouse model.The interaction of active components and P-gp / BCRP will be studied under the physiological condition, AD pathological condition and drug administration, using AD animal model and in vivo microdialysis sampling. Meanwhile, the protein expression of P-gp and BCRP will be measured and the neuro-transmitters will be determined by HPLC-QQQ-MS.The transport mechanism across BBB as well as the distribution of active components in Zhimu / Danshen , is supposed to be elucidated. All work attempts to establish feasible and new quantitative evaluation system on the basis of TCM active components, endogenous neuro-transmitters and drug transporters, and therefore accelerates the new drug development for AD and provides scientific support for CNS drug research and the drug-drug interaction.