目的 采用代謝組學(xué)技術(shù)，研究藥根堿對葡聚糖硫酸鈉（dextran sulfate sodium，DSS）誘導(dǎo)的潰瘍性結(jié)腸炎（ulcerative colitis，UC）小鼠內(nèi)源代謝物的影響，探討其代謝途徑及作用機(jī)制。方法 雄性C57BL/6小鼠，隨機(jī)分為對照組、模型組、美沙拉嗪（0.3 g/kg）組和藥根堿低、高劑量（40、80 mg/kg）組，每組10只，連續(xù)7 d ig美沙拉嗪及藥根堿，同時自由飲用3% DSS溶液誘導(dǎo)潰瘍性結(jié)腸炎模型。通過疾病活動指數(shù)（disease activity index，DAI）、血清生化指標(biāo)、結(jié)腸病理組織染色明確藥根堿治療潰瘍性結(jié)腸炎的藥理作用。收集小鼠結(jié)腸組織進(jìn)行非靶向代謝組學(xué)分析，標(biāo)定差異代謝物與特征通路，探究藥根堿治療潰瘍性結(jié)腸炎的代謝通路作用機(jī)制。結(jié)果 與對照組比較，模型組小鼠DAI評分顯著升高（P＜0.01），血清中腫瘤壞死因子-α（tumor necrosis factor-α，TNF-α）、白細(xì)胞介素-6（interleukin-6，IL-6）、IL-16和IL-1β水平均顯著升高（P＜0.01）；與模型組比較，給予藥根堿后，上述指標(biāo)顯著降低（P＜0.05、0.01），且高劑量效果更明顯。同時藥根堿能夠改善UC小鼠結(jié)腸黏膜充血與水腫、緩解結(jié)腸萎縮、減輕結(jié)腸出血的癥狀。非靶向代謝組學(xué)結(jié)果顯示，與對照組比較，模型組磷脂酰膽堿、膽酸、鵝去氧膽酸、PE [14:0/20:1(11Z)]、高香草醛含量顯著降低（P＜0.01），但花生四烯酸和松柏醇含量顯著升高（P＜0.01）；上述差異代謝物含量經(jīng)過藥根堿干預(yù)后明顯回調(diào)（P＜0.05、0.01）。結(jié)論 藥根堿能夠下調(diào)相關(guān)炎癥因子，調(diào)節(jié)花生四烯酸代謝和甘油磷脂代謝等通路的代謝紊亂，恢復(fù)結(jié)腸屏障，改善DSS誘導(dǎo)的潰瘍性結(jié)腸炎。

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.

R285.5

國家自然科學(xué)基金資助項(xiàng)目（82304738）;四川省科技計(jì)劃資助（2024NSFSC1835）;西華大學(xué)人才引進(jìn)項(xiàng)目（Z211060）