目的 探究赶黄草Penthorum chinense对原发性硬化性胆管炎（primary sclerosing cholangitis，PSC）的改善作用及其潜在机制。方法 采用超高效液相色谱-串联质谱（ultra-performance liquid chromatography-tandem mass spectrometry，UPLC-MS/MS）对赶黄草提取物中的成分进行分析。将50只小鼠随机分为对照组、模型组、奥贝胆酸（6.5 mg/kg）组和赶黄草低、高剂量（2、4 g/kg）组，每组10只。小鼠给予0.1% 3,5-二乙氧基羰基-1,4-二氢可力丁（3,5-diethoxycarbonyl-1,4-dihydrocollidine，DDC）饲料喂养以诱导PSC模型，给药干预14 d后，通过检测血清生化指标、肝组织病理变化及肝纤维化标志物评估赶黄草的药效作用。进一步通过转录组测序、qRT-PCR实验及胆汁酸谱定量分析探讨其作用机制。结果 赶黄草提取物中共鉴定出331种化学成分。药效学结果显示，与模型组比较，高剂量的赶黄草能显著降低小鼠肝脏指数及血清肝损伤指标水平（P＜0.05、0.01、0.001），并有效改善肝组织胆汁淤积和纤维化，效果优于阳性对照药奥贝胆酸。转录组学分析筛选出51个差异表达基因，富集分析提示赶黄草的作用与胆汁分泌等通路相关。机制验证表明，与模型组比较，高剂量的赶黄草能显著下调小鼠肝脏中初级胆汁酸合成关键酶的mRNA表达（P＜0.05），同时上调胆汁酸结合酶的表达（P＜0.001）。血清及肝脏中胆汁酸谱分析显示，高剂量的赶黄草干预后，结合型/非结合型胆汁酸比例显著增加（P＜0.001）。结论 赶黄草可通过抑制初级胆汁酸合成、促进其结合化及排泄，从而有效缓解DDC诱导的胆汁淤积性肝损伤，对PSC具有改善作用。

Objective To investigate the therapeutic effect and potential mechanism of Penthorum chinense (PCP) on primary sclerosing cholangitis (PSC). Methods The chemical constituents of PCP extract were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A total of 50 mice were randomly divided into control group, model group, obeticholic acid (6.5 mg/kg) group and PCP low-, high-dose (2, 4 g/kg) groups, with 10 mice in each group. Mice were fed with 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feed to induce PSC model. After 14 d of intervention, the efficacy of PCP was evaluated by measuring serum biochemical indicators, liver histopathological changes and liver fibrosis markers. To further explore the mechanisms, transcriptomic sequencing, qRT-PCR experiment and quantitative analysis of bile acid profile were performed. Results A total of 331 chemical constituents were identified in PCP extract. Pharmacodynamic results showed that compared with model group, high-dose PCP significantly reduced liver index and levels of liver injury markers in serum (P < 0.05, 0.01, 0.001), and effectively alleviated cholestasis and fibrosis in liver tissue, with effects superior to those of positive drug obeticholic acid. Transcriptomic analysis identified 51 differentially expressed genes. Enrichment analysis suggested that the effect of PCP was associated with pathways such as bile secretion. Mechanistic validation revealed that compared with model group, high-dose PCP significantly down-regulated mRNA expressions of key enzymes for primary bile acid synthesis in liver tissue (P < 0.05), while up-regulated expression of bile acid‑conjugating enzyme (P < 0.001). Serum and liver bile acid profiling revealed that high-dose PCP intervention significantly increased the ratio of conjugated to unconjugated bile acids (P < 0.001). Conclusion PCP ameliorates DDC‑induced cholestatic liver injury and exerts a therapeutic effect on PSC by inhibiting primary bile acid synthesis, promoting bile acid conjugation and excretion.

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北京市自然科学基金项目（7214282）；民族医药教育部重点实验室项目（KLEM-ZZ202401）；质谱成像与代谢组学国家民委重点实验室项目（KLMSIM202301）；中央民族大学研究生科研项目（SZKY-X2025094）