基于肠道菌群和代谢组学探究升阳益胃汤抗溃疡性结肠炎的作用机制

李葳; 王英杰; 王仁嫒; 李积良

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李葳, 王英杰, 王仁嫒, 李积良.基于肠道菌群和代谢组学探究升阳益胃汤抗溃疡性结肠炎的作用机制[J].湖南中医药大学学报英文版,2026,46(8):1548-1558.[Click to copy ]

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基于肠道菌群和代谢组学探究升阳益胃汤抗溃疡性结肠炎的作用机制

李葳,王英杰,王仁嫒,李积良

(青海大学医学院中医系, 青海西宁 810016;青海省糖脂代谢疾病防控中医药重点实验室, 青海西宁 810016;青海省中医院肛肠科, 青海西宁 810016)

摘要:

目的基于肠道菌群与血清代谢组学，观察升阳益胃汤对三硝基苯磺酸（TNBS）诱导的溃疡性结肠炎（UC）模型大鼠的干预效果，探究其改善肠道炎症与肠黏膜屏障的作用机制。方法将70只SPF级雄性大鼠随机分为空白组、模型组、美沙拉秦组和升阳益胃汤低、中、高剂量组，每组10只。采用TNBS灌肠法构建UC模型，造模成功后，美沙拉秦组予美沙拉秦药液灌胃（0.2 g/kg），升阳益胃汤低、中、高剂量组分别予升阳益胃汤水煎液（6.3、12.6、25.2 g/kg）灌胃，空白组、模型组予等量生理盐水灌胃。每日1次，持续干预7 d。干预期间监测各组大鼠的体质量、粪便性状及便隐血情况以计算疾病活动指数（DAI）；ELISA检测超氧化物歧化酶（SOD）、还原型谷胱甘肽（GSH）、一氧化氮（NO）、丙二醛（MDA）；HE染色和阿尔辛蓝-过碘酸希夫（AB-PAS）染色观察结肠组织病理变化；16S rRNA测序分析肠道菌群多样性与结构变化；非靶向代谢组学分析血清差异代谢物及富集通路；Western blot检测结肠组织Occludin、Claudin-1蛋白表达水平。结果与空白组相比，模型组DAI评分及血清MDA、NO水平升高（P<0.01），血清SOD、GSH水平及结肠组织中Occludin、Claudin-1蛋白表达水平均降低（P<0.05，P<0.01）。与模型组相比，升阳益胃汤高剂量组和美沙拉秦组DAI评分及血清MDA、NO水平降低（P<0.01），血清SOD、GSH水平及结肠组织中Occludin和Claudin-1蛋白表达水平升高（P<0.05，P<0.01）。与升阳益胃汤低剂量组相比，升阳益胃汤高剂量组和美沙拉秦组DAI评分及血清MDA、NO水平均降低（P<0.01），SOD、GSH水平和结肠组织Occludin、Claudin-1蛋白表达水平均升高（P<0.05，P<0.01）。与空白组相比，模型组结肠黏膜结构损伤、炎症细胞大量浸润、杯状细胞数量减少；肠道菌群多样性紊乱，芽孢杆菌门丰度下调、拟杆菌门及变形菌门丰度上调，乳杆菌属等有益菌群丰度降低；血清代谢轮廓改变，影响ABC转运蛋白、生物素代谢、辅因子生物合成、胆汁分泌等通路。经过升阳益胃汤干预后，结肠黏膜损伤、炎症浸润及杯状细胞损伤得到有效修复；乳杆菌属、粘液乳杆菌属等丰度回升，鼠杆菌科等丰度下降；血清代谢紊乱得到调控，筛选出114个药物干预相关差异代谢物，主要影响胆碱代谢相关、甘油磷脂代谢、α-亚麻酸代谢、酪氨酸代谢及胆汁分泌等通路。结论升阳益胃汤可有效改善UC大鼠肠道炎症与氧化应激损伤，修复肠黏膜屏障，其干预效应可能与调节肠道菌群稳态、重塑血清代谢紊乱存在关联。

DOI：10.3969/j.issn.1674-070X.2026.08.002

Received:July 06, 2026

基金项目:青海省卫生健康系统指导性计划课题（2025-wjzdx-34）。

Mechanism of action of Shengyang Yiwei Decoction against ulcerative colitis based on gut microbiota and metabolomics

LI Wei, WANG Yingjie, WANG Ren'ai, LI Jiliang

(Department of Traditional Chinese Medicine, Medical College, Qinghai University, Xining, Qinghai 810016, China;Qinghai Provincial Key Laboratory of Traditional Chinese Medicine for Prevention and Control of Glucolipid Metabolic Diseases, Xining, Qinghai 810016, China;Department of Proctology, Qinghai Provincial Hospital of Traditional Chinese Medicine, Xining, Qinghai 810016, China)

Abstract:

Objective To observe the therapeutic effects of Shengyang Yiwei Decoction (SYYWD) on trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis (UC) model rats based on gut microbiota and serum metabolomics, and to explore its mechanism of action in alleviating intestinal inflammation and improving intestinal mucosal barrier function. Methods Seventy SPF male rats were randomly divided into a blank group, a model group, a mesalazine group, and low-, medium-, and high-dose SYYWD groups, with 10 rats in each group. The UC model was established by TNBS enema. After successful modeling, the mesalazine group received mesalazine suspension (0.2 g/kg) by gavage, the low-, medium-, and high-dose SYYWD groups received corresponding doses of SYYWD (6.3, 12.6, and 25.2 g/kg, respectively) by gavage, and the blank and model groups were given equal volumes of normal saline. All treatments were administered once daily for 7 consecutive days. During the intervention period, body weight, fecal consistency, and fecal occult blood of rats in each group were monitored, and the disease activity index (DAI) was calculated. The levels of superoxide dismutase (SOD), reduced glutathione (GSH), nitric oxide (NO), and malondialdehyde (MDA) were detected by ELISA. Hematoxylin-eosin (HE) staining and Alcian blue-periodic acid-Schiff (AB-PAS) staining were performed to observe the histopathological changes of colonic tissue. The diversity and community structure of gut microbiota were analyzed by 16S rRNA gene sequencing. Untargeted metabolomics was performed to identify serum differential metabolites and enriched metabolic pathways. Western blot was used to detect the protein expression levels of Occludin and Claudin-1 in colonic tissue. Results Compared with the blank group, the model group showed elevated DAI scores and serum MDA and NO levels (P<0.01), and reduced serum SOD and GSH levels as well as the protein expression levels of Occludin and Claudin-1 in colonic tissue (P<0.05, P<0.01). Compared with the model group, the high-dose SYYWD group and the mesalazine group showed decreased DAI scores and serum MDA and NO levels (P<0.01), and increased serum SOD and GSH levels as well as Occludin and Claudin-1 protein expression in colonic tissue (P<0.05, P<0.01). Compared with the low-dose SYYWD group, the high-dose SYYWD group and the mesalazine group also showed decreased DAI scores and serum MDA and NO levels (P<0.01), and increased SOD and GSH levels as well as Occludin and Claudin-1 protein expression in colonic tissue (P<0.05, P<0.01). Compared with the blank group, the model group exhibited disrupted colonic mucosal structure, extensive infiltration of inflammatory cells, and a reduced number of goblet cells. The gut microbiota showed dysbiosis, with downregulated abundance of Bacillota, upregulated abundance of Bacteroidetes and Proteobacteria, and decreased abundance of beneficial genera such as Lactobacillus. Serum metabolic profiles were altered, affecting pathways including ABC transporters, biotin metabolism, cofactor biosynthesis, and bile secretion. After intervention with SYYWD, the colonic mucosal damage, inflammatory infiltration, and goblet cell injury were effectively restored. The abundance of genera such as Lactobacillus and Limosilactobacillus was increased, while the abundance of Muribaculaceae decreased. Serum metabolic disorders were modulated, with 114 drug intervention-related differential metabolites identified, mainly affecting pathways associated with choline metabolism, glycerophospholipid metabolism, α-linolenic acid metabolism, tyrosine metabolism, and bile secretion. Conclusion SYYWD can effectively alleviate intestinal inflammation and oxidative stress injury in UC rats, repair the intestinal mucosal barrier, and its therapeutic effects may be associated with regulating gut microbiota homeostasis and ameliorating serum metabolic disorders.

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