目的 研究厚樸溫中湯及其配方顆粒治療脾胃虛寒型胃病的作用及機制。方法 采用豬油和冷食醋造模10 d，構(gòu)建大鼠脾胃虛寒型胃病模型，分別給予厚樸溫中湯煎湯（Houpo Wenzhong Decoction，DEC）、配方顆粒（formula granules，GRA）、煎湯加輔料（decoction with accessories，ACC）治療7 d。ELISA法檢測大鼠血清胃動素（motilin，MTL）和胃泌素（gastrin，GAS）含量；16S rRNA高通量測序技術(shù)進行大鼠腸道菌群多樣性分析，超高效液相色譜-四極桿-飛行時間串聯(lián)質(zhì)譜（ultra performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry，UPLC-Q-TOF-MS/MS）開展尿液和糞便的代謝組學(xué)研究，并結(jié)合Spearman分析進行腸道菌群與代謝組學(xué)之間的關(guān)聯(lián)分析。結(jié)果 與模型組比較，DEC與GRA均可顯著升高大鼠體質(zhì)量、血清MTL及GAS含量（P＜0.05、0.01、0.001）。16S rRNA測序結(jié)果顯示，DEC和GRA均可顯著調(diào)控乳酸桿菌屬、嗜木聚糖真桿菌群、毛螺菌科NK4A136群、羅氏菌屬、未分類鼠桿菌科、活潑瘤胃球菌群、副沙門氏菌屬的水平（P＜0.05、0.01）。尿液、糞便代謝組學(xué)各篩選出脾胃虛寒生物標志物32、39個，其中在DEC組與GRA組中共同發(fā)現(xiàn)脾胃虛寒生物標志物17α,21-二羥基孕烯醇酮、melibiitol、膽固醇乙酸酯、7α-羥基-3-氧代-4-膽甾烯酸酯。代謝通路分析顯示，DEC、GRA通過調(diào)控尿液中的類固醇激素生物合成、苯丙氨酸代謝、維生素B₆代謝等通路，糞便中的類固醇生物合成、卟啉代謝等通路來發(fā)揮抗脾胃虛寒的作用。Spearman分析發(fā)現(xiàn)部分腸道差異菌群與尿液、糞便中差異代謝物之間存在密切的關(guān)聯(lián)性。結(jié)論DEC、GRA改善脾胃虛寒型胃病的作用機制可能與調(diào)控腸道菌群組成和類固醇合成、氨基酸代謝等相關(guān)通路有關(guān)，且二者在生化指標、腸道菌群、代謝組學(xué)方面基本一致，因此厚樸溫中湯配方顆粒臨床替用傳統(tǒng)煎湯具有可行性。

Objective To investigate the mechanism of Houpo Wenzhong Decoction (厚樸溫中湯) 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

國家自然科學(xué)基金資助項目（82160731）；江西中醫(yī)藥大學(xué)校級科技創(chuàng)新團隊發(fā)展計劃（CXTD22007）；江西省科技創(chuàng)新基地（20242BCC32062）；江西省研究生創(chuàng)新專項項目（YC2024-B221）