基于“广义质控组分”和“七情对照谱效关联追踪”的三棱质量评价研究

In order to develop a new method of quality evaluations which is based on theories of TCM, agreement with clinical application, and helpful to enhancing security and effectiveness, “Broad quality compositions” is proposed in the light of regularities of compound herbal formulae. “Spectrum-effect tracing according to relationships of different combinations” is proposed on the basis of connections among “original components”, “oral components”, and “ingested components”. Sparganii Rhizoma will be used to treated blood-stasis rats models alone, combined with Curcumae Rhizoma, or combined with Natrii Sulfas. Chromatography and chromatographic hyphenated techniques will be used to study chemical changes. Spectrum-activity relationships will be studied by SVM and multiple regression with anticoagulant aggregation and coagulation as the Indicators. After the relations among “original components”，“oral components” and “ingested components” are interpreted, “broad quality compositions” in three levels (using alone, good compatibility, bad compatibility) will be confirmed Finally, evaluation methods and indicators will be establish. This project will provide scientific basis for its further development and utilization, quality evaluation and to ensure the clinical effectiveness and safety. It is also important to inherit and develop theories of TCM.

为探索基于中医药理论、符合临床用药规律、有助于提高药材安全性和有效性的质量评价方法，基于七情配伍理论提出“广义质控组分”的新假说，并且依据药材中“原型成分”、服用药剂中“临床成分”以及发挥作用的“入血成分”之间的关联性提出“七情对照谱效关联追踪”的新方法。在前期研究的基础上，以三棱为例，选择单行、与莪术相须、与芒硝相恶三种代表性配伍；采用多种色谱及联用技术表征药材“原型成分”、三种配伍样本“临床成分”和大鼠血瘀模型中“入血成分”的化学指纹信息；以抗血小板聚集和凝血四项为药效指标，利用支持向量机等方法进行多维“七情对照谱效关联追踪”。在三种配伍对照和体内外关联性研究中，追踪出三棱药材中“单行显效、配伍增效、配伍禁忌”三个层次的“广义质控组分”，建立适宜的定性定量方法和评价指标。本研究为三棱全面品质评价、开发利用及指导临床用药提供依据，对中医药理论的继承和发展也具有重要意义。

本课题经三棱（生／醋／与莪术配伍的药对）不同极性部位的抗血栓作用研究发现水部位的抗凝活性最强，醇部位的抗血小板聚集作用最佳；利用HPLC分别建立三棱（生／醋／药对）水煎液和醇提液的化学指纹图谱及多成分的定量分析方法；利用LC-MS建立三棱（生／醋／药对）入血成分的定量分析方法；对照分析发现三棱与莪术配伍时多种酚酸及醛类成分含量增加，与芒硝配伍时含量降低；与三棱（生／醋／药对）水煎液、醇提液、入血成分的谱效关系分析表明对香豆酸、阿魏酸、香草酸等多种酚醛类成分为其活性物质；代谢组学分析发现与三棱干预相关的差异代谢物生化途径主要涉及氨基酸、糖、脂质等代谢通路。本课题的研究方法结合炮制配伍规律进行对照分析，可以相互验证、补充从而修正、完善实验结论；本课题的研究结果有利于完善三棱质量标准、阐明炮制配伍机理。