目的 研究厚朴温中汤及其配方颗粒治疗脾胃虚寒型胃病的作用及机制。方法 采用猪油和冷食醋造模10 d，构建大鼠脾胃虚寒型胃病模型，分别给予厚朴温中汤煎汤（Houpo Wenzhong Decoction，DEC）、配方颗粒（formula granules，GRA）、煎汤加辅料（decoction with accessories，ACC）治疗7 d。ELISA法检测大鼠血清胃动素（motilin，MTL）和胃泌素（gastrin，GAS）含量；16S rRNA高通量测序技术进行大鼠肠道菌群多样性分析，超高效液相色谱-四极杆-飞行时间串联质谱（ultra performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry，UPLC-Q-TOF-MS/MS）开展尿液和粪便的代谢组学研究，并结合Spearman分析进行肠道菌群与代谢组学之间的关联分析。结果 与模型组比较，DEC与GRA均可显著升高大鼠体质量、血清MTL及GAS含量（P＜0.05、0.01、0.001）。16S rRNA测序结果显示，DEC和GRA均可显著调控乳酸杆菌属、嗜木聚糖真杆菌群、毛螺菌科NK4A136群、罗氏菌属、未分类鼠杆菌科、活泼瘤胃球菌群、副沙门氏菌属的水平（P＜0.05、0.01）。尿液、粪便代谢组学各筛选出脾胃虚寒生物标志物32、39个，其中在DEC组与GRA组中共同发现脾胃虚寒生物标志物17α,21-二羟基孕烯醇酮、melibiitol、胆固醇乙酸酯、7α-羟基-3-氧代-4-胆甾烯酸酯。代谢通路分析显示，DEC、GRA通过调控尿液中的类固醇激素生物合成、苯丙氨酸代谢、维生素B₆代谢等通路，粪便中的类固醇生物合成、卟啉代谢等通路来发挥抗脾胃虚寒的作用。Spearman分析发现部分肠道差异菌群与尿液、粪便中差异代谢物之间存在密切的关联性。结论DEC、GRA改善脾胃虚寒型胃病的作用机制可能与调控肠道菌群组成和类固醇合成、氨基酸代谢等相关通路有关，且二者在生化指标、肠道菌群、代谢组学方面基本一致，因此厚朴温中汤配方颗粒临床替用传统煎汤具有可行性。

Objective To investigate the mechanism of Houpo Wenzhong Decoction (厚朴温中汤) and its formula granules in treatment of gastropathy with spleen and stomach deficiency cold type, and provide a reference for evaluating the potential of formula granules as substitutes for traditional decoction. Methods Houpo Wenzhong Decoction (DEC), formula granules (GRA) and decoction with accessories (ACC) were used to treat the model rats of gastropathy with spleen and stomach deficiency cold type for 7 d, which was established by lard and cold vinegar for 10 d. The levels of motilin (MTL) and gastrin (GAS) in serum of rats were detected by ELISA. Gut microbiota diversity of rats was detected by 16S rRNA high-throughput sequencing technology, and then metabolomics in urine and feces were researched by ultra performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Finally, the correlation between gut microbiota and metabolomics was analyzed through Spearman’s analysis. Results Compared with model group, the body weight (P < 0.05) and levels of MTL and GAS in serum (P < 0.01, 0.001) of rats were significantly increased both in DEC group and GRA group. The results of 16S rRNA sequencing indicated that Lactobacillus, Eubacterium_xylanophilum_group, Lachnospiraceae_NK4A136_group, Roseburia, norank_f_Muribaculaceae, Ruminococcus_ gnavus_group and Parasutterella (P < 0.05, 0.01) were significantly regulated after treatment with DEC or GRA. A total of 32 biomarkers related to spleen and stomach deficiency cold were identified in urine, while 39 biomarkers were identified in feces. Notably, shared metabolites such as 17α,21-dihydroxypregnenolone, melibiitol, cholesterol acetate and 7α-hydroxy-3-oxo-4-cholestenoate were found together in DEC and GRA groups. Metabolic pathway analysis indicated that DEC or GRA played an important role in regulating pathways such as steroid hormone biosynthesis, phenylalanine metabolism and vitamin B6 metabolism in urine, as well as steroid biosynthesis and porphyrin metabolism in feces. In addition, Spearman’s correlation analysis also revealed that there was a strong correlation between some intestinal differential flora and differential metabolites in urine and feces. Conclusion The mechanism by which DEC and GRA improve gastropathy with spleen and stomach deficiency cold type may be related to the regulation of gut microbiota composition and pathways related to steroid synthesis and amino acid metabolism. Overall, DEC and GRA are basically the same in biochemical indexes, gut microbiota, and metabolomics. Thus, GRA may be suitable for clinical use as an alternative to traditional decoction.

R285.5

国家自然科学基金资助项目（82160731）；江西中医药大学校级科技创新团队发展计划（CXTD22007）；江西省科技创新基地（20242BCC32062）；江西省研究生创新专项项目（YC2024-B221）