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基于转录组学和胆汁酸谱探讨赶黄草改善原发性硬化性胆管炎的作用机制

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中草药 | 药理与临床 2026,57(6): 2144-2157

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中草药 |药理与临床 2026 , 57 (6) : 2144 -2157

基于转录组学和胆汁酸谱探讨赶黄草改善原发性硬化性胆管炎的作用机制

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阿茹罕¹, 苦阿华¹, 李晓宁¹, 李雨鑫¹, 吉荣¹, 张紫珺¹, 宋彬彬¹

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作者简介:

阿茹罕: 阿茹罕,硕士研究生,研究方向为中药民族药防治肝病。E-mail:aruhan1126@163.com 苦阿华: 苦阿华,硕士研究生,研究方向为中药民族药防治肝病。E-mail:akushiqing@163.com

Mechanism of Penthorum chinense in alleviating primary sclerosing cholangitis based on transcriptomic and bile acid profiling

A Ruhan, KU Ahua, LI Xiaoning, LI Yuxin, JI Rong, ZHANG Zijun, SONG Binbin

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doi: 10.7501/j.issn.0253-2670.2026.06.013

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摘要

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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。

关键词

赶黄草 / 原发性硬化性胆管炎 / 胆汁分泌 / 转录组学 / 胆汁酸 / 没食子酸 / 3-吲哚丙烯酸 / 6-羟基山柰酚-7-O-葡萄糖苷

Abstract

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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.

Key words

Penthorum chinense Pursh / primary sclerosing cholangitis / bile secretion / transcriptomics / bile acid / gallic acid / 3-indolepropionic acid / 6-hydroxykaempferol-7-O-glucoside

引用本文

阿茹罕, 苦阿华, 李晓宁, 李雨鑫, 吉荣, 张紫珺, 宋彬彬. 基于转录组学和胆汁酸谱探讨赶黄草改善原发性硬化性胆管炎的作用机制. 中草药, 2026 , 57 (6) : 2144 -2157 . DOI: 10.7501/j.issn.0253-2670.2026.06.013

A Ruhan, KU Ahua, LI Xiaoning, LI Yuxin, JI Rong, ZHANG Zijun, SONG Binbin. Mechanism of Penthorum chinense in alleviating primary sclerosing cholangitis based on transcriptomic and bile acid profiling[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (6) : 2144 -2157 . DOI: 10.7501/j.issn.0253-2670.2026.06.013

基金

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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)

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2026年第57卷第6期

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doi: 10.7501/j.issn.0253-2670.2026.06.013

接收时间：2025-12-19
首发时间：2026-09-09

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收稿日期：2025-12-19

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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