目的 通过药效学和肝脏代谢组学相结合，探讨芪葛汤配伍前后对降脂作用的影响，为探索中药配伍的 科学内涵提供新的研究策略。方法 根据药效组策略，将三组给药组设置为芪葛汤组、黄芪-葛根药对（君臣药 效）组和广陈皮（佐药效）组。采用血脂 4 项、血清生化指标及肝脏形态病理学评价高脂血症大鼠模型和芪葛汤 的干预作用；运用肝脏代谢组学技术分析芪葛汤配伍前后对代谢产物的影响，结合多元统计分析评估各组之间 在差异代谢物和代谢途径的角度上的差异。结果 与模型组比较，芪葛汤组的血脂 4 项指标回调能力均高于药 对组和广陈皮组，其中，芪葛汤组的总胆固醇（TC）、甘油三酯（TG）水平降低（P＜0.05）。肝脏代谢组学共鉴定 出 86 个潜在生物标记物，芪葛汤组、黄芪-葛根药对组和广陈皮组回调代谢物分别有 23、13 和 7 个，差异有 统计学意义（P＜0.05）。将 29 个出现显著回调作用的特异性生物标志物进行代谢路径分析，结果显示与甘油磷 脂代谢、亚油酸代谢、α-亚麻酸代谢、鞘脂代谢、花生四烯酸代谢、不饱和脂肪酸的生物合成通路有关。其 中，芪葛汤主要调节甘油磷脂和亚油酸代谢，并且独特作用于鞘脂代谢。结论 芪葛汤配伍后具有更多的降脂 靶点，降脂的作用优于药对组及广陈皮组，为深入揭示中医组方配伍的科学内涵提供了实验依据和研究策略。

Objective To explore the lipid-lowering effect of Qige Decoction before and after compatibility through the combination of pharmacodynamics and liver metabolomics，and to provide new research strategies for exploring the scientific notation of traditional Chinese medicine compatibility. Methods According to the pharmacodynamic strategy，three groups of drug administration were set up as Qige Decoction group，Astragali Radix-Puerariae Radix group，and Pericarpium Citri Tangerinae group. Four indices of blood lipids，serum biochemical indicators，and liver morphology and pathology were used to evaluate the intervention effect of Qige Decoction on hyperlipidemic rats. Liver metabolomics technology was used to analyze the effects of Qige Decoction on metabolites before and after compatibility，and multivariate statistical analysis was used to evaluate the differences between groups in terms of differential metabolites and metabolic pathways. Results Compared with the model group，the callback abilities of four indices of blood lipid in the Qige Decoction group were higher than those in Astragali Radix-Puerariae Radix group and Pericarpium Citri Tangerinae group， among which the total cholesterol （TC） and triglyceride （TG） levels in the Qige Decoction group decreased （P＜0.05）. A total of 86 potential biomarkers were identified by liver metabolomics，with 23，13，and 7 metabolites being significantly different in the Qige Decoction group，Astragali Radix-Puerariae Radix group，and Pericarpium Citri Tangerinae group，respectively （P＜0.05）. Metabolic pathway analysis of 29 specific biomarkers with significant callback effects showed that they were related to glycerophospholipid metabolism，linoleic acid metabolism，α-linolenic acid metabolism，sphingolipid metabolism， arachidonic acid metabolism， and unsaturated fatty acid biosynthesis. Qige Decoction mainly regulates glycerophospholipid and linoleic acid metabolism，and uniquely acts on sphingolipid metabolism. Conclusion Qige Decoction has more lipid-lowering targets after compatibility， with better lipid-lowering effects than the Astragali Radix-Puerariae Radix group and Pericarpium Citri Tangerinae group. This study provides experimental evidence and research strategies for further revealing the scientific notation of traditional Chinese medicine compatibility.

R285.5

国家自然科学基金项目（82074099）；广东省基础与应用基础研究基金（2023A1515011126）；广州中医药大学“双一流”与高水平大学 学科协同创新团队项目（2021xk33）；广东省中医药科研项目（20231171）。