【作者】 李秀玲；

【导师】 梁鑫淼；

【作者基本信息】 中国科学院研究生院（大连化学物理研究所） ， 分析化学， 2003， 博士

【摘要】 中药复方是中医用药的主要形式，而配伍理论是中药复方的根本。为了充分发挥中药复方的优势，采用现代科学和技术研究中药复方配伍，阐明复方药效的物质基础及作用原理是十分必要的。本论文针对中药配伍研究中存在的问题，研究了精致血府逐瘀方剂配伍的化学成分变化、药理变化及其药效物质基础，为方剂的现代化研究奠定了基础。 论文提出中药复方配伍全成分研究的总体思路。首先需要建立一套稳定、可靠、重现性好、有较好的分离度和适当分离时间的色谱分离方法；其次应用保留时间、紫外光谱和分子量等信息明确归属配伍后化学成分的来源；最后比较配伍前后化学成分的含量的变化。在方法研究的基础上，首次研究了精致血府逐瘀方剂中药对和药队配伍全成分的变化情况。药对和药队配伍后，既有化学成分含量的变化又有新成分的产生。 在配伍的药理研究方面，利用大鼠高脂模型首次研究了精制血府逐瘀复方及方中不同药对和不同提取方法对脂质代谢、血小板功能、白细胞活化表达率、血液粘度、血管活性物质和红细胞功能的影响。结果表明，精致血府逐瘀方剂及方中不同药对可作用于引起动脉粥样硬化的不同环节，配伍后的疗效在某些方面有一定增加：不同提取方法的药物作用环节作用也不尽相同。在细胞药理方面，研究组分及组分配伍后对Ox-LDL导致的细胞损伤的保护作用和对NO的升高作用。不同组分及组分配伍对细胞的保护作用和NO的升高作用不同。 应用HPLC-MS／MS首次定性和定量分析大鼠给服精制血府逐瘀复方以及方中药对给药后血清中的多种化学成分。首次应用HPLC-MS／MS研究赤芍中的甙类化合物，定性21个已知的甙类；并发现赤芍中化合物的种类和相应化合物的含量都高于白芍。还应用HPLC-MS／MS研究不同组分提取物中的成分，在一定程度上阐明了药效物质基础。更多还原

【Abstract】 Prescriptions are the main form of traditional Chinese medicines (TCMs). Theory of compatibility is the essential part of TCM prescriptions. In order to develop the advantages of TCM, it is necessary to clarify the effective substances of TCM by means of modern science and technology. In this paper, the refined Xuefuzhuyu (XFZHY) prescription was taken as an example to study the chemical changes of all components, pharmacological changes and the effective compounds in the compatibility. It laid a foundation for the modernization of TCMs.In this paper, the comprehensive design of studying overall chemical components in TCM compatibility was put forward for the first time. For the complex system as herbs, a good separation method was developed firstly, which included reproducibility, proper resolution and retention times. Separation mode, column, mobile phases and operating parameters were optimized to reach this goal. Then, information of retention time, ultraviolet spectra (UV) and molecular weight were used to confirm the origin of peaks in co-decoction. Finally, Chemical changes of components in TCM compatibility were compared. On the basis of this study, three herb couples and one herb team in refined XFZHY under different extraction conditions were studied to find their chemical changes. The results indicated that some components changed in content after compatibly mixing. Whereas, only one regenerate component was found in the ethanol extracts of Ligusticum wallichii, Radices paeoniae rubra herb couple and the water extracts of Bupleurum falcatom L, Radices paeoniae rubra herb couple.In order to study the compatibility in pharmacology, high-fat model of rats was used to investigate the effects of refined XFZHY prescription, different herb couples and herb teams to different pharmacological indexes, which include blood fat,platelet function, leukocyte activity, blood viscosity, vaso-active substrate and akaryocyte function. The effects of different extracts of refined XFZHY prescription and its different herb couples to blood fat, platelet function and vaso-active substrate were also studied. The pharmacological results indicated that these herbs could act on different aspects of arteriosclerosis. The curative effects after compatibly mixing were enhanced to some aspects. Effects of different extracts were not exactly the same. Furthermore, different extracts of effective compounds were investigated on cell. Three effective compounds could protect the damage induced by Ox-LDl and two of them could improve the contents of NO remarkably.Based on the pharmacological study, for the first time HPLC-MS/MS was used to study multiple components in rat serum after administrating different herb couples and herb teams in the XFZHY. Some components in rat serum were qualitatively analysed, while three flavonoids were quantitatively analysed. HPLC-MS/MS was also applied for the qualitative analysis of glycoside components in the extracts of Radix paeonia rubra (RPR) and a total of 21 glycosides were identified. It is indicated that both the number and contents of components in RPR were higher than those of RPA by using HPLC-MS/MS for studying differences between Radices paeoniae alba (RPA) and Radices paeoniae rubra (RPR). The extracts of effective compounds were investigated by HPLC-MS/MS. To some extent, the effective substances of prescription compatibility were clarified.更多还原