血脑屏障药物筛选模型的建立及丹参活性成分筛选分析  

Establishment of blood-brain barrier model and its application to the screening of active components from Danshen extracts

作　　者：原江锋[1,2,3] 崔军见[1,2] 尚卫[1,2] 刘建利[1,2] 张志琪[1,2] 

机构地区：[1]药用植物资源与天然药物化学教育部重点实验室 [2]陕西师范大学化学与材料科学学院,西安710062 [3]河南科技大学食品与生物工程学院,洛阳471003

出　　处：《中国科学：化学》2010年第6期717-724,共8页SCIENTIA SINICA Chimica

基　　金：国家自然科学基金(20575039,20875060);教育部高等学校博士点学科专项科研基金(20050718011)资助

摘　　要：ECV304细胞在C6细胞的诱导下生长,通过细胞培养时间优化、渗透系数测定和细胞形态学观察等,建立ECV304/C6共培养血脑屏障(BBB)药物筛选模型.将该模型应用于从丹参提取液中筛选可能作用于中枢神经系统(CNS)的活性成分,结合液相色谱-质谱联用技术(LC-MS)分析,发现丹参提取液中至少有16种成分能够穿越BBB模型,其中4种成分被确认为隐丹参酮、丹参酮Ⅰ、丹参素和原儿茶酸.通过定量构效关系(QASR)分析,进一步从理论上证明所确认的4种化合物均符合CNS靶向药物的特征.研究结果表明,ECV304/C6共培养BBB模型能够在模拟生理状态下从中药复杂体系中筛选分离跨越BBB的活性成分组,可用于CNS药物开发的早期快速筛选,服务于中药现代化研究.A blood-brain barrier（BBB） model for the screening of drug candidates was established by means of ECV304/C6 co-culture.The permeability parameters and morphological analysis showed that the cultured ECV304 cell monolayer was of integrity and vitality.The active components of widely used medicinal plant Danshen（Salvia miltiorrhiza） were screened with BBB model,and then analyzed and elucidated with LC-MS.The results indicated that 16 compounds at least,in Danshen extracts,could permeate over BBB model,in which cryptotanshinone,tanshinone I,danshensu and protocatechuic acid were deduced and identified.Quantitative structure activity relationship analysis further showed that the identified 4 compounds were consistent with the rules for central nervous system drug-like molecules.This result demonstrated that the combination of ECV304/C6 co-culture model with LC-MS analysis should be an attractive and great potential method for the screening of central nervous system drug candidates from traditional Chinese medicine.

关 键 词：血脑屏障(BBB)模型 药物筛选 LC-MS 丹参 中药 QASR分析 

分 类 号：R285[医药卫生—中药学]