基于在线微透析技术的益智仁治疗AD入血/脑药效物质高通量识别与作用机制研究

阿尔茨海默病（AD）是威胁老年人健康的严重疾病之一，益智仁作为治疗AD疗效确切的中药，其体内药效物质基础和作用机制尚不明确。本课题以中药整体观、多组分和多层次协同作用特征作为切入点，在前期对益智仁萜类化学成分研究基础上，将先进的在线微透析采样技术和定性能力强、灵敏度高的组合质谱检测技术结合起来，在AD大鼠全血透析液和脑脊液两个通道同时研究益智仁入血/脑的萜类成分原形及代谢物，并采用质谱一级精确准分子离子全扫描模式高通量追踪这些成分在体内的动态变化，对同时入血和脑的萜类成分通过制备液相分离出来，并以Aβ为靶点初步研究其活性；最后通过代谢组技术，在大鼠内源性代谢物网络变化层面系统探讨药物的治疗机制，以达到揭示益智仁治疗AD的药效物质基础和作用机制的目的, 研究成果将为益智仁治疗AD的现代化研究提供新的思路和科学依据。

Alzheimer's disease (AD) is one of the serious diseases threatening the health of the elderly. And as a kind of Traditional Chinese Medicine (TCM)which has an obvious therapeutic effect on AD, the material basis and mechanism of fructus alpinae oxyphyllae is still unclear at present. The comprehensive, synergy of multi-component and multi-level of TCM will be regarded as the breakthrough point, and the advanced microdialysis technology combined with the combining mass spectrometry which has the strong qualitative ability and high sensitivity will be used to make a study on the prototype and metabolites of the terpenoid compounds existing in blood/brain from two channels included the whole blood dialysate and cerebrospinal fluid collected from AD rats. The dynamic change of these ingredients in vivo is tracked by the first-order precise molecular ion full scanning model and the high content ingredients will be separated by the preparative liquid chromatograph. Then the Aβ will be treated as a target to make a preliminary study of the ingredients activity and the metabolomics will be used to explore the therapeutic mechanism of the drug through the network change of the endogenous metabolites in rats. After the above steps, revealing the material basis and therapeutic mechanism of fructus alpinae oxyphyllae will be achieved in the end. And this research result will provide new ideas and scientific basis for the modern researches of fructus alpinae oxyphyllae’s therapeutic effect on AD.