数字中医药（英文）2026，Vol.9Issue(1)：114-129,16.DOI:10.1016/j.dcmed.2026.02.010
半夏泻心汤通过调节肠道菌群缓解小鼠食管癌前病变的机制研究
Attenuation of esophageal precancerous lesions in mice by Banxia Xiexin Decoction through gut microbiota modulation
摘要
Abstract
Objective To investigate the microbial mechanisms of Banxia Xiexin Decoction(半夏泻心汤,BXXXD)in the treatment of esophageal precancerous lesions. Methods A total of 30 specific pathogen-free(SPF)grade female C57BL/6J mice were ran-domly assigned to a control group(n=6)and a 4-nitroquinoline 1-oxide(4-NQO)-exposed group(n=24).Esophageal precancerous lesions were induced by providing the 4-NQO-ex-posed group with 4-NQO in drinking water(100 μg/mL)for 17 consecutive weeks,whereas control group received sterile drinking water.After model establishment,the mice in 4-NQO-exposed group were further randomized into model group and three BXXXD-treated groups:low-dose(BXXXD-L,3.7 g/kg),medium-dose(BXXXD-M,7.4 g/kg),and high-dose(BXXXD-H,14.8 g/kg)groups(n=6 per group).During the subsequent intervention period,mice in control and model groups were gavaged with sterile water,while mice in BXXXD groups were gavaged once daily with the corresponding dose of BXXXD aqueous extract for 4 weeks.Histopathological changes in esophageal tissues were observed by hematoxylin and eosin(HE)staining.The fecal and esophageal microbiota were profiled via 16S rDNA high-through-put sequencing to evaluate bacterial diversity,community structure,and co-occurrence net-works.BXXXD chemical fingerprints were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole QExactive Orbitrap mass spectrometry(UHPLC-QE-MS).Serum short-chain fatty acids(SCFA)level was quantified by targeted metabolomics using gas chromatography-mass spectrometry(GC-MS).Transcriptomic analysis of esophageal tissues was performed to assess gene expression profiles. Results Compared with model group,BXXXD-M group exhibited reduced mucosal hyperpla-sia and more orderly epithelial cell arrangement,with superior therapeutic effects in compar-ison with both BXXXD-L and BXXXD-H groups(P<0.01).Microbiota analysis revealed that BXXXD increased the abundance of beneficial Enterococcus and reduced pathogenic Es-cherichia-Shigella in the esophagus.In the gut,BXXXD elevated the relative abundance of beneficial taxa,including Lactobacillus,Dubosiella,Bacteroides,and Faecalibacterium.Tar-geted metabolomics showed that BXXXD significantly reduced total serum SCFA level(P<0.01).Transcriptomic analysis indicated that BXXXD downregulated the expression of genes associated with the progression,migration,and invasion of esophageal cancer,which were identified as kallikrein-related peptidase 6(Klk6),defensin beta 4(Defb4),family with sequence similarity 3 member B(Fam3b),carboxypeptidase A4(Cpa4),serum amyloid A1(Saa1),and chitinase-like 1(Chil1)(P<0.05). Conclusion BXXXD may reduce the expression levels of esophageal cancer-related genes and improve esophageal precancerous lesions through modulation of the gut microbiota and metabolites.关键词
半夏泻心汤/食管癌前病变/肠道菌群/转录组/短链脂肪酸Key words
Banxia Xiexin Decoction/Esophageal precancerous lesions/Gut microbiota/Transcriptome/Short-chain fatty acids引用本文复制引用
靳曼,朱雯菲,王召玲,虞快,吴剑平,张军峰..半夏泻心汤通过调节肠道菌群缓解小鼠食管癌前病变的机制研究[J].数字中医药（英文）,2026,9(1):114-129,16.基金项目
National Natural Science Foundation of China(82274369). （82274369）
