目的 探究泻白散中佐使药甘草和粳米配伍的合理性和科学性。方法 按照古代工艺制备泻白散，采用UPLC-Q-Exactive-MS/MS技术，对泻白散全方、缺甘草方、缺粳米方、缺甘草和粳米方样品开展化学成分研究，确定共有化学成分和差异化学成分，以泻白散全方化学成分为基础，以共有桑白皮和地骨皮的化学成分为研究对象，进行成分归类研究，通过计算各类成分峰面积占总峰面积的相对权重，研究4组样品中化学成分种类的动态变化规律，结合主成分分析（principal component analysis，PCA）和正交偏最小二乘法-判别分析（orthogonal partial least squares-discriminant analysis，OPLS-DA）筛选影响显著变化的化学成分，确定甘草和粳米药对在泻白散中配伍后化学成分种类的变化和影响变化的差异成分，确定差异化合物。结果 泻白散全方共鉴定化学成分158个，包括黄酮类、有机酸类、生物碱类、三萜类及皂苷类、香豆素类、杂环、苯及取代物类、核苷类、酚类、醌类、有机氧化物类以及其他类共13类化合物。其中158个成分中归属于共有药材桑白皮、地骨皮的化学成分125个，经筛选后确定差异成分22个。粳米能促进有机酸类、酚类化合物溶出，抑制黄酮类、生物碱类、其他类化合物的溶出。甘草能促进黄酮类、生物碱类、酰胺类化合物的溶出，抑制有机酸类和杂环类化合物的溶出，甘草和粳米对黄酮类和生物碱类有相互制衡的作用。缺甘草和粳米方与泻白散全方对比，黄酮类、生物碱类相对权重降低，可见甘草和粳米配伍后泻白散化学成分发生变化，根据PCA和OPLS-DA结果，以变量重要性投影（variable importance in projection，VIP）值＞1为筛选条件，确定影响成分变化的28主要种差异化学成分，包括boldenone undecylenate、甜菜碱、桑皮苷A、L-焦谷氨酸、L-脯氨酸、地骨皮甲素等。结论 泻白散中甘草和粳米配伍具有合理性和科学性，二者配伍有助于方中黄酮类和生物碱类成分释放均衡，故甘草和粳米对泻白散处方药味加减缺一不可，为后续泻白散处方研究及制剂研发奠定基础。

Objective Explore the rationality and scientificity of the compatibility of the assistant and envoy herbs, Gancao (Glycyrrhizae Radix et Rhizoma, GRR) and Jingmi (Oryzae Sativae Semen, OSS), in Xiebai San (泻白散). Methods Prepare Xiebai San according to ancient craftsmanship. Utilize UPLC-Q-Exactive-MS/MS technology to conduct a study on the chemical components of samples of the complete Xiebai San formula, the formula lacking GRR, the formula lacking OSS, and the formula lacking both GRR and OSS. Identify the common chemical components and the differential chemical components. Based on the chemical constituents of the complete Xiebai Powder formula, the chemical constituents of the shared Sangbaipi (Mori Cortex) and Digupi (Lycii Cortex) were used as the research objects to carry out the constituent categorization study, and by calculating the relative weights of the peak areas of each type of constituents to the total peak area, we studied the dynamic change pattern of the types of chemical constituents in the four groups of samples, and combined with the principal component analysis (PCA) and the orthogonal partial least squares-discriminant analysis (OPLS-DA) to screen for the influence of the significant changes of the chemical components, to determine the changes in chemical component species and the differential components affecting the changes after the pairing of licorice and japonica rice in diarrhea white powder, and to identify the differential compounds. Results A total of 158 chemical components were identified in the complete Xiebai San formula, including 13 classes of compounds such as flavonoids, organic acids, alkaloids, triterpenoids and saponins, coumarins, heterocycles, benzene and its substitutes, nucleosides, phenols, quinones, organic oxides, and others. Among the 158 components, 125 chemical components were attributed to the common herbs Mori Cortex and Lycii Cortex, and 22 differential components were identified after screening. OSS can promote the dissolution of organic acids and phenols while inhibiting the dissolution of flavonoids, alkaloids, and other compounds. GRR can promote the dissolution of flavonoids, alkaloids, and amides while inhibiting the dissolution of organic acids and heterocycles. GRR and OSS have a mutually restrictive effect on flavonoids and alkaloids. Compared with the complete Xiebai San formula, the relative weights of flavonoids and alkaloids decreased in the formula lacking both GRR and OSS. It can be seen that the chemical components of Xiebai San changed after the compatibility of GRR and OSS. According to the results of PCA and OPLS-DA, with the variable importance in projection (VIP) value > 1 as the screening criterion, 28 main differential chemical components that affect the component changes were determined, including boldenone undecylenate, betaine, mulberroside A, L-pyroglutamic acid, L-proline, and kukoamine A. Conclusion The compatibility of GRR and OSS in Xiebai San is rational and scientific. Their combination helps to achieve a balanced release of flavonoids and alkaloids in the formula. Therefore, both GRR and OSS are indispensable when adding or subtracting herbs in the Xiebai San prescription. This study lays a foundation for subsequent research on the Xiebai San prescription and the development of its preparations.

R283.6

国家青年科学基金项目（82404842）