基于体内自组装胶束形成机制的羊脂油炙淫羊藿增效机理研究

Research hypothesis: Suet oil promotes the self-assembled nanomicelles to form when Epimedium fried with suet oil is taken orally into the body, increasing the solubility of the active flavonoids, and improving the intestinal absorption of the active flavonoids, which plays its synergistic effect..The processing effect of fried Epimedium can be divided into two key aspects: one is the role of processing accessories "suet oil", the other is the role of "hot" during processing. The first two National Natural Science Foundation items have clarified the role and mechanism of the "hot" factor during processing with ADME for the first time: heating promotes Epimedium to produce more absorbable bioactivity flavonoids. This project will further explain the role and synergistic mechanism of processing accessories "suet oil" based on it promoting self-assembled micelles formation in vivo after oral administration of fried Epimedium..This project will study the effect and mechanism of Epimedium active flavonoids self-assembled micelles formed by suet oil to promote intestinal absorption, using Caco-2 cell model and single-pass rat intestinal perfusion model in vivo as well as plasma concentration method and pharmacological effects method in pharmacokinetics. This project will also study the synergistic effect and mechanism of Epimedium flavonoids self-assembled micelles on kidney-yang deficiency rats as well as on the hypothalamic-pituitary-adrenal-thymus axis. From the whole animal, tissue, cellular and molecular levels, this project will elucidate the scientific meaning of traditional accessories processing theory about Epimedium fried with suet oil.

研究假说：炙淫羊藿口服进入体内，羊脂油促进了纳米胶束的自组装形成，增加了活性黄酮的溶解度，提高了活性黄酮的肠吸收，从而发挥了其增效作用。.炙淫羊藿炮制作用可分为炮制辅料"羊脂油"和炮制过程"热"的作用两个关键环节。前两项国家自然科学基金项目首次从ADME角度阐明了炮制过程中"热"的因素作用与机制：加热使淫羊藿产生了更多易于吸收的生物活性黄酮；本项目进一步从炙淫羊藿口服后羊脂油促进了"自组装胶束"的体内形成，阐述炮制辅料"羊脂油"的作用与增效机理。.采用Caco-2细胞模型与大鼠在体单向肠灌流模型、以及药动学血药浓度法与药理效应法，研究淫羊藿活性黄酮在羊脂油作用下形成的自组装胶束促进肠吸收的作用与机制，并研究淫羊藿黄酮自组装胶束对肾阳虚大鼠的增效作用以及对下丘脑-垂体-肾上腺-胸腺轴的作用机制；从整体动物、组织、细胞和分子水平，深层次阐明羊脂油炙淫羊藿传统辅料炮制理论的科学内涵。

炙淫羊藿炮制作用可分为炮制辅料“羊脂油”和炮制过程“热”的作用两个关键环节。前两项国家自然科学基金项目首次从ADME角度阐明了炮制过程中“热”的因素作用与机制，本项目进一步从炙淫羊藿口服后羊脂油促进“自组装胶束”的体内形成，阐述炮制辅料“羊脂油”的作用与增效机理。研究证实在羊脂油的作用下，淫羊藿黄酮可自组装形成胶束，增加其溶解度，促进肠吸收，提高体内生物利用度，从而发挥羊脂油的增效作用。淫羊藿黄酮自组装形成胶束后对大鼠的“肾阳虚”证具有增效作用，且与大鼠下丘脑-垂体-肾上腺-胸腺轴以及主要性腺组织睾丸的病理改变和功能改善有密切关系。.本项目从整体动物、组织、细胞和分子水平层面上分别深层次阐明了羊脂油炙淫羊藿传统炮制辅料炮制理论的科学内涵，创新性从药剂学角度阐述羊脂油炙淫羊藿的炮制机理，为中药炮制机理的研究提供了新思路与新方法，对揭示中药“油炙”的科学内涵具有重要的理论意义和应用价值。并在国内外主流期刊（中文为核心期刊）上发表论文31篇，其中SCI源刊14篇；会议交流论文13篇；培养博士生2名，硕士生6名，为中药炮制培养了一批优秀的科研人才。