建立以血小板聚集途径为识别元件的生物传感体系探究益气活血方剂药效机制

As Supplening Qi and Activating Blood formule, QiShenYiQi drop pills is the modern traditional chinese medicine made up of the valuable component of Panax notoginseng, Radix Salvia miltiorrhiza Bge, Radix Astragalus membranaceus Bge, and Dalbergia odorifera T.Che. Large-scale clinical experiments conform that QiShenYiQi drop pills has the same effects in the secondary treatment of myocardial infarction (MI) as Aspirin, but the mechanism of action is still unclear. We assume that it may act on several blood platelet aggregation pathways cooperated with several components, which is called " regulating mutliple components, integrating small effects ". So it can inhibit blood platelet aggregation and then take effects in the secondary treatment of MI. This project plans to adopt biosensor technology to confirm the assumption. The previous work has proved in methodology that biosensor technology has the advantage of time and cost in the traditional medicine mechnism research, especially about the action pathway of medicine after synergy and the action target screening. The project selects three important pathways and targets related to blood platelet aggregation as the recognition elements: Cyclooxygenase metabolizing arachidonic acid pathway, platelet activating factors and its receptor, and platelet membrane glycoprotein GPⅡb／Ⅲa. Compared with the traditional mechinism research of chinese medicine, we try to explain the molecular-level action mechnism of QiShenYiQi drop pills in the secondary treatment of MI by constructing biosensor real-time detection system and hyperlipoidemia animal model. As a result, it will be possible to supply a new modern biology method in researching the pharmaco-mechanism of QiShenYiQi drop pills.

益气活血方剂- - 芪参益气滴丸是由黄芪、丹参、三七、降香有效组分组方的现代中药。大规模临床试验证实，它与阿司匹林对心肌梗死二级预防效应相当，但作用机理尚不明确。我们设想其可能是通过多组分协同作用于多条血小板聚集途径，"多因微效、整合调节"，起到抑制血小板聚集的作用，从而发挥心肌梗死二级预防的疗效。本项目拟采用生物传感技术证实这一假说，前期工作已从方法学上证明，将生物传感技术应用于中药药理研究、尤其是药物配伍后的作用途径及靶点甄选具有时间和成本的优势。本项目针对性地选取三条与血小板聚集相关的重要途径和靶点- - 环氧化酶代谢花生四烯酸途径、血小板活化因子及其受体、血小板膜糖蛋白GPⅡb／Ⅲa为识别元件，构建实时监测生物传感研究体系，结合高脂血症动物模型，并与传统中药药理研究方法对比验证，力图从分子水平阐释芪参益气滴丸抗血小板聚集效应及作用机制，为益气活血方剂药效机制研究提供一种新的现代生物学方法。

益气活血方剂——芪参益气滴丸是由黄芪、丹参、三七、降香有效组分组方的现代中药。大规模临床试验证实，它与阿司匹林对心肌梗死二级预防效应相当，但作用机理尚不明确。本项目通过综合运用传统药理学研究方法和生物传感技术，运用催化型和亲和型生物传感仪器，同时构建高血脂血症动物模型，辅以其他现代生物学实验手段，针对性的选取了三个与血小板聚集相关的重要途径，基于环氧化酶代谢花生四烯酸途径、基于血小板活化因子活化途径、基于血小板膜糖蛋白GPⅡb/Ⅲa途径，构建了可用于研究芪参益气滴丸抗血小板聚集效应的生物传感研究体系，尝试从分子水平阐释其“多因微效、整合调节”的作用机制，为益气活血方剂药效机制研究提供一种新的现代生物学方法，同时，将生物传感技术应用于中药药理研究以及药物配伍作用途径和靶点的甄选是对中药传统药理研究方法的有益补充，具有十分重要的现实意义。