目的 采用代谢组学技术，研究药根碱对葡聚糖硫酸钠（dextran sulfate sodium，DSS）诱导的溃疡性结肠炎（ulcerative colitis，UC）小鼠内源代谢物的影响，探讨其代谢途径及作用机制。方法 雄性C57BL/6小鼠，随机分为对照组、模型组、美沙拉嗪（0.3 g/kg）组和药根碱低、高剂量（40、80 mg/kg）组，每组10只，连续7 d ig美沙拉嗪及药根碱，同时自由饮用3% DSS溶液诱导溃疡性结肠炎模型。通过疾病活动指数（disease activity index，DAI）、血清生化指标、结肠病理组织染色明确药根碱治疗溃疡性结肠炎的药理作用。收集小鼠结肠组织进行非靶向代谢组学分析，标定差异代谢物与特征通路，探究药根碱治疗溃疡性结肠炎的代谢通路作用机制。结果 与对照组比较，模型组小鼠DAI评分显著升高（P＜0.01），血清中肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-6（interleukin-6，IL-6）、IL-16和IL-1β水平均显著升高（P＜0.01）；与模型组比较，给予药根碱后，上述指标显著降低（P＜0.05、0.01），且高剂量效果更明显。同时药根碱能够改善UC小鼠结肠黏膜充血与水肿、缓解结肠萎缩、减轻结肠出血的症状。非靶向代谢组学结果显示，与对照组比较，模型组磷脂酰胆碱、胆酸、鹅去氧胆酸、PE [14:0/20:1(11Z)]、高香草醛含量显著降低（P＜0.01），但花生四烯酸和松柏醇含量显著升高（P＜0.01）；上述差异代谢物含量经过药根碱干预后明显回调（P＜0.05、0.01）。结论 药根碱能够下调相关炎症因子，调节花生四烯酸代谢和甘油磷脂代谢等通路的代谢紊乱，恢复结肠屏障，改善DSS诱导的溃疡性结肠炎。

Objective To investigate the effect of jatrorrhizine on endogenous metabolites in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice using metabolomics technology, and to explore its metabolic pathway and mechanism of action. Methods Male C57BL/6 mice were randomly divided into control group, model group, 5-amino salicylic acid (5-ASA, 0.3 g/kg) group, jatrorrhizine low dose (40 mg/kg), and high dose (80 mg/kg) groups, with 10 mice in each group. Mice were intragastrically administered with 5-ASA or jatrorrhizine for seven consecutive days, while freely drinking with 3% DSS solution to induce an UC model. The pharmacological effects of jatrorrhizine on UC were determined through disease activity index (DAI), serum biochemical indicators, and colon pathological tissue staining. Mice colon tissue was collected for untargeted metabolomics analysis. Differential metabolites and characteristic pathways were calibrated, and the metabolic pathway mechanism of jatrorrhizine in treating UC was further explored.Results Compared with the control group, the DAI score of the model group mice was significantly increased (P < 0.01), and the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-16 and IL-1β in serum were significantly increased (P < 0.01). After administration of jatrorrhizine, compared with the model group, the above indicators significantly decreased (P < 0.05, 0.01), and the effect was more pronounced at high doses. Simultaneously, jatrorrhizine had effect on improving congestion and edema of the colon mucosa in mice, alleviating colon atrophy, and reducing colon bleeding. Untargeted metabolomics results showed that compared with the control group, the levels of phosphatidylcholine, cholic acid, chenodeoxycholic acid, PE [14:0/20:1(11Z)], and homovanillin were significantly reduced in the model group (P < 0.01), but the levels of arachidonic acid and coniferyl alcohol were significantly increased (P < 0.01). The differential metabolite levels mentioned above were significantly overturned after intervention with jatrorrhizine (P < 0.05, 0.01). Conclusion Jatrorrhizine has effect on downregulating related inflammatory factors, regulating metabolic disorders in pathways such as arachidonic acid metabolism and glycerophospholipid metabolism, restoring the colon barrier, and improving DSS-induced UC.

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国家自然科学基金资助项目（82304738）;四川省科技计划资助（2024NSFSC1835）;西华大学人才引进项目（Z211060）