目的 探讨大黄、桃仁配伍前后“逐瘀泻热”协同增效的作用及作用机制。方法 建立大黄-桃仁水提物的含量测定方法，将大鼠随机分为对照组、模型组、大黄组、桃仁组和大黄-桃仁组，干预给药21 d后依据Schwartzman反应原理复制“瘀热”大鼠模型，通过血液流变，凝血四项及肝脏、肾脏组织病理学变化评估大黄、桃仁配伍前后的“逐瘀泻热”作用。采用UPLC-Q-TOF-MS代谢组学技术及16S rRNA高通量测序技术分析各组大鼠血浆代谢产物和肠道菌群的变化。结果 所建立的HPLC法可同时测定大黄-桃仁水提物中10种化学成分的含量；药效学研究表明大黄、桃仁、大黄-桃仁均有明显的“逐瘀泻热”功效，且配伍后该功效增强，同时，给药后改善了肝、肾炎症及充血等病理情况。代谢组学结果显示，大黄、桃仁可能通过富马酸、γ-氨基丁酸、L-谷氨酰胺等差异代谢物调控苯丙氨酸代谢、β-丙氨酸代谢、蛋白质的消化和吸收等通路发挥协同增强“逐瘀泻热”的功效。16S rRNA结果显示，配伍桃仁能够削弱大黄对变形菌门、拟杆菌属、志贺氏菌属等相对丰度的影响，配伍大黄能够削弱桃仁对拟杆菌门的影响，2药配伍能够增强疣微菌门、经黏液真杆菌属、普雷沃氏菌属等的相对丰度，减少异杆菌属相对丰度，使厚壁菌门的相对丰度维持平衡。结论 大黄、桃仁“逐瘀泻热”协同增效的疗效可能与改善肠道菌群组成，影响苯丙氨酸代谢、β-丙氨酸代谢、蛋白质的消化和吸收等代谢通路有关。

Objective To investigate the synergistic effect and mechanism of removing blood stasis and purging heat before and after the compatibility of Dahuang (Rhei Radix et Rhizoma) and Taoren (Persicae Semen). Methods A method for determining the content of water extract of Rhei Radix et Rhizoma-Persicae Semen was established. The rats were randomly divided into control group, model group, Rhei Radix et Rhizoma group, Persicae Semen group and Rhei Radix et Rhizoma-Persicae Semen group. After 21 d of intervention, “stasis heat” rat model was replicated according to the Schwartzman reaction principle. The effect of removing blood stasis and purging heat before and after the compatibility of Rhei Radix et Rhizoma and Persicae Semen was evaluated by hemorheology, coagulation of four items, and liver and kidney histopathological changes. UPLC-Q-TOF-MS metabolomics technology and 16S rRNA high-throughput sequencing technology were used to analyze the plasma metabolites and intestinal flora changes in each group. Results The established HPLC method could simultaneously determine the contents of 10 chemical components in water extract of Rhei Radix et Rhizoma-Persicae Semen. Rhei Radix et Rhizoma, Persicae Semen, and Rhei Radix et Rhizoma-Persicae Semen had the obvious effect of removing blood stasis and purging heat, and the effect was enhanced after compatibility. At the same time, the pathological conditions such as liver and kidney inflammation and congestion were improved after administration. The results of metabolomics showed that Rhei Radix et Rhizoma and Persicae Semen may regulate phenylalanine metabolism, β-alanine metabolism, protein digestion and absorption through fumaric acid, γ-aminobutyric acid, L-glutamine and other differential metabolites to play a synergistic effect of removing blood stasis and purging heat. The results of 16S rRNA showed that the compatibility of Persicae Semen could weaken the effect of Rhei Radix et Rhizoma on the relative abundance of Proteobacteria, Bacteroides and Shigella. The compatibility of Rhei Radix et Rhizoma could weaken the effect of Persicae Semen on Bacteroides. The compatibility of the two drugs could enhance the relative abundance of Verrucomicrobia, Myxomycetes and Prevotella, reduce the relative abundance of Heterobacter, and maintain the relative abundance of Firmicutes. Conclusion The synergistic effect of Rhei Radix et Rhizoma and Persicae Semen in removing blood stasis and purging heat may be related to improving the composition of intestinal flora, affecting metabolic pathways such as phenylalanine metabolism, β-alanine metabolism, protein digestion and absorption.

R285.5

国家自然科学基金资助项目（81973592）；陕西省中医药管理局项目（2021-GJ-JC004）；陕西中医药大学“秦药”品质评价与资源开发学科创新团队项目（2019-QN01）