基于肠道菌群-色氨酸代谢-芳香烃受体轴探讨黄芩汤改善溃疡性结肠炎的作用机制
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| 篇名: | 基于肠道菌群-色氨酸代谢-芳香烃受体轴探讨黄芩汤改善溃疡性结肠炎的作用机制 |
| TITLE: | Mechanism of Huangqin decoction in improving ulcerative colitis based on the gut microbiota-tryptophan metabolism-aryl hydrocarbon receptor axis |
| 摘要: | 目的 探讨黄芩汤通过肠道菌群-色氨酸代谢-芳香烃受体(AhR)轴改善溃疡性结肠炎(UC)的机制。方法将小鼠随机分为正常组(生理盐水)、模型组(生理盐水)、菌群消耗-模型组(生理盐水)、菌群消耗-黄芩汤组(9.1g/kg,以生药量计;下同)、黄芩汤组及美沙拉嗪组(阳性对照组,0.4g/kg),每组6只。通过自由饮用抗菌药物混合液10d消耗菌群,自由饮用2.5%葡聚糖硫酸钠溶液7d构建UC模型。造模成功后,各组小鼠灌胃相应药液/生理盐水,每天1次,连续10d。末次给药后,测定小鼠体重变化比、疾病活动指数(DAI)评分、结肠长度,观察结肠病理学变化,检测血清中白细胞介素6(IL-6)、IL-10、IL-22、肿瘤坏死因子α(TNF-α)含量以及结肠组织中闭合蛋白(Occludin)、闭锁小带蛋白1(ZO-1)、AhR的表达,并对小鼠粪便进行高通量测序和色氨酸靶向代谢组学分析。结果与模型组比较,黄芩汤组小鼠结肠组织炎症细胞浸润减少,肠黏膜结构恢复;体重变化比、结肠长度、血清中IL-10含量和结肠组织中Occludin、ZO-1、AhR表达水平以及色氨酸代谢物吲哚-3-丙酸(IPA)、N-乙酰-5-羟色胺(NAS)、吲哚-3-乙酸(IAA)含量均显著升高/增加(P<0.05);DAI评分以及血清中IL-6、TNF-α、IL-22含量和色氨酸代谢物吲哚-3-乙醇含量均显著降低(P<0.05);肠道菌群结构改善,乳杆菌属等有益菌的相对丰度呈升高趋势,大肠埃希氏菌-志贺氏菌属等致病菌的相对丰度呈降低趋势。然而,抗菌药物消耗菌群后,黄芩汤虽能显著升高小鼠粪便中NAS含量,但结肠组织中AhR蛋白表达未同步显著回升。结论黄芩汤可通过调控肠道菌群,促进IPA、IAA产生,从而激活AhR,进而修复UC小鼠肠黏膜屏障;完整肠道菌群是黄芩汤发挥AhR调控作用的重要前提。 |
| ABSTRACT: | OBJECTIVE To investigate the mechanism of Huangqin decoction in improving ulcerative colitis (UC) through the gut microbiota-tryptophan metabolism-aryl hydrocarbon receptor (AhR) axis. METHODS Mice were randomly divided into normal group (normal saline), model group (normal saline), microbiota depletion-model group (normal saline), microbiota depletion-Huangqin decoction group (9.1 g/kg, by crude drug, similarly hereinafter), Huangqin decoction group and mesalazine group (positive control group, 0.4 g/kg), with 6 mice in each group. Microbiota depletion was achieved by providing free access to a mixed antibiotics for 10 days. The UC model was induced by administering 2.5% dextran sulfate sodium solution for 7 days. After successful modeling, each treatment group received corresponding drugs or normal saline intragastrically once daily for 10 days. After the final administration, body weight change ratio, disease activity index (DAI) score, and colon length were evaluated; colon pathological changes were observed; serum levels of interleukin-6 (IL-6), IL-10, IL-22, and tumor necrosis factor-α (TNF-α) were measured; the expressions of Occludin, zonula occluden-1 (ZO-1), and AhR in colon tissue were detected; fecal samples were subjected to high-throughput sequencing to analyze targeted tryptophan metabolomics. RESULTS Compared with the model group, Huangqin decoction group showed reduced infiltration of inflammatory cells in the colon tissue and restoration of the intestinal mucosal structure. Body weight change ratio, colon length, serum content of IL-10, the expressions of Occludin, ZO-1 and AhR in colon tissue and the contents of tryptophan metabolites indole-3-propionic acid (IPA), N -acetylserotonin (NAS) and indole-3-acetic acid (IAA) were all significantly increased ( P <0.05); DAI score, serum levels of IL-6, TNF-α, and IL-22 and the content of tryptophan metabolite indole-3-ethanol were significantly decreased ( P <0.05); gut microbiota structure was improved, with increased relative abundances of beneficial bacteria such as Lactobacillus , and decreased relative abundances of pathogenic bacteria such as Escherichia-Shigella . However, after antibiotic-induced microbiota depletion, although Huangqin decoction significantly increased the content of NAS in the feces of mice, the expression of AhR protein in colon tissue did not increase concurrently. CONCLUSIONS Huangqin decoction can repair the intestinal mucosal barrier in UC mice by regulating the gut microbiota and promoting the production of IPA and IAA, thereby activating AhR. This suggests that an intact gut microbiota is an important prerequisite for Huangqin decoction to exert its AhR-regulating effects. |
| 期刊: | 2026年第37卷第09期 |
| 作者: | 陈颖;徐荣;何瑶;李英;张之雨;吴至久 |
| AUTHORS: | CHEN Ying,XU Rong,HE Yao,LI Ying,ZHANG Zhiyu,WU Zhijiu |
| 关键字: | 黄芩汤;溃疡性结肠炎;肠道菌群;色氨酸代谢;芳香烃受体 |
| KEYWORDS: | Huangqin decoction; ulcerative colitis; gut microbiota; tryptophan metabolism; aryl hydrocarbon receptor |
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