目的 评价9种归脾经中药（白扁豆、当归、大枣、黄芪、红参、龙眼肉、玫瑰花、人参、山楂）对小鼠脾脏代谢组及肠道菌群的调控作用，为归脾经中药的作用机制研究与分类评价提供参考。方法 9种归脾经中药分为3类：补气健脾类5种（白扁豆、大枣、黄芪、红参、人参）、补血养血类2种（当归、龙眼肉）、理气化滞类2种（玫瑰花、山楂）。C57BL/6JGpt小鼠随机分为10组，分别为对照组、白扁豆（5.85 g·kg^-1）组、当归（4.68 g·kg^-1）组、大枣（5.85 g·kg^-1）组、黄芪（11.70 g·kg^-1）组、红参（3.51 g·kg^-1）组、龙眼肉（5.85 g·kg^-1）组、玫瑰花（2.34 g·kg^-1）组、人参（3.51 g·kg^-1）组、山楂（4.68 g·kg^-1）组，每组8只，各处理组分别ig给予各中药水煎液，对照组给予等量的去离子水，每天1次，连续10 d。采用脾脏组织非靶向代谢组学结合肠道菌群16S rRNA基因测序技术检测脾脏代谢谱与肠道菌群组成的变化，并通过Spearman相关性分析揭示菌群-代谢物关联模式。结果 9种归脾经中药干预后，脾脏代谢谱均发生不同程度改变，3组样本整体代谢构成具有较高同质性，脂质占优势地位，其中补血养血类脂肪酰基占比略高，理气化滞类有机氧化合物相对富集。各组差异代谢物富集通路涉及甘油磷脂代谢、脂肪酸生物合成、三羧酸循环及氨基酸代谢等多个功能类别，不同功效类别呈现差异化调控特征：补气健脾类对甘油磷脂代谢调控效应突出，补血养血类侧重脂肪酸代谢通路，理气化滞类对氧化应激相关通路作用更强。各类中药分别富集特定差异菌属，且菌群与脾脏代谢物存在广泛显著关联，其中脂质代谢类（脂肪酰基、甘油磷脂）与菌群的关联最为突出。结论 不同功效归脾经中药存在“共性核心通路＋功效特异性偏向”的调控模式，从肠-脾轴角度为归经理论的现代生物学诠释提供了组学层面的实验参考。

Objective To evaluate the regulatory effects of nine Chinese medicinal herbs for spleen meridian tropism (Lablab album Semen, Angelicae Sinensis Radix, Jujubae Fructus, Astragali Radix, Red Ginseng, Longan Arillus, Rosae Rugosae Flos, Panax Ginseng, Crataegi Fructus) on spleen metabolome and gut microbiota in mice, and to provide experimental evidence for the mechanism research and classification evaluation of spleen meridian tropism herbs. Methods Nine spleen-tonifying Chinese herbs were classified into three categories: five qi-supplementing and spleen-strengthening herbs (Lablab album Semen, Jujubae Fructus, Astragali Radix, Red Ginseng, Rosae Rugosae Flos), two blood-nourishing herbs (Angelicae Sinensis Radix, Longan Arillus), and two qi-regulating and stagnation-resolving herbs (Rosae Rugosae Flos, Crataegi Fructus). C57BL/6JGpt mice were randomly divided into ten groups: a control group and nine treatment groups administered with aqueous extracts of the respective herbs at doses of 5.85 g·kg^-1 for Lablab album Semen, 4.68 g·kg^-1 for Angelicae Sinensis Radix, 5.85 g·kg^-1 for Jujubae Fructus, 11.70 g·kg^-1 for Astragali Radix, 3.51 g·kg^-1 for Red Ginseng, 5.85 g·kg^-1 for Longan Arillus, 2.34 g·kg^-1 for Rosae Rugosae Flos, 3.51 g·kg^-1 for Panax Ginseng, and 4.68 g·kg^-1 for Crataegi Fructus. Each group consisted of eight mice. The treatment groups received their respective herbal decoctions via ig once daily for 10 consecutive days, while the control group received an equal volume of deionized water. Spleen metabolite profiles and gut microbiota composition were analyzed using untargeted metabolomics combined with 16S rRNA gene sequencing. Spearman correlation analysis was used to identify associations between microbial communities and metabolites. Results After intervention with the nine spleen-tonifying herbs, the spleen metabolome changed to varying degrees. The overall metabolic profiles of the three herb categories exhibited high homogeneity, dominated by lipids—particularly fatty acyls in the blood-nourishing category and organic oxides enriched in the qi-regulating category. Differentially expressed metabolites were enriched in multiple functional pathways, including glycerophospholipid metabolism, fatty acid biosynthesis, tricarboxylic acid cycle, and amino acid metabolism. Distinct regulatory patterns emerged across different herb categories: The qi-supplementing and spleen-strengthening herbs significantly influenced glycerophospholipid metabolism; the blood-nourishing herbs primarily affected fatty acid metabolism; and the qi-regulating herbs exerted stronger effects on oxidative stress-related pathways. Each herb group also enriched specific differential bacterial genera, and significant correlations were widely observed between gut microbiota and spleen metabolites, particularly strong links between lipid metabolism-related compounds (fatty acyls and glycerophospholipids) and microbial communities. Conclusion Chinese medicinal herbs with different efficacies for spleen meridian tropism exhibit a regulatory pattern of “common pathway categories plus efficacy-specific biases”, providing omics-level experimental evidence for the modern biological interpretation of meridian tropism theory from the perspective of the gut-spleen axis.

R965

河北省科学院科技计划项目（26B302）