时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
Furthermore, patients with PSC face a significantly elevated risk of hepatobiliary malignancies, most notably cholangiocarcinoma, which remains a primary driver of mortality in this cohort., The precise etiology and molecular pathogenesis of PSC remain elusive, despite decades of intensive clinical and translational research.；However, the specific signaling pathways that bridge chronic inflammation to biliary injury and progressive fibrosis have yet to be fully elucidated.；The expression of NQO1 is primarily governed by nuclear factor erythroid 2-related factor 2 (Nrf2) during oxidative stress or by aryl hydrocarbon receptor (AhR) in response to xenobiotics., Although NQO1 has demonstrated protective effects in various inflammatory liver diseases by mitigating ROS-induced injury, its functional significance in the context of PSC remains largely uncharacterized.
方法
Male WT or NKO mice, aged 8–10 weeks, were utilized in this study.；All animal experiments were conducted in accordance with the institutional guidelines for the care and use of laboratory animals and were approved by the Institutional Animal Care and Use Committee of the Korea Research Institute of Bioscience and Biotechnology (KRIBB-AEC-23065 and KRIBB-AEC-24194).；Furthermore, variations in the total bile acid (TBA) concentrations induced by DDC were quantified using a commercial TBA assay kit (Sigma-Aldrich) in strict accordance with the provider’s guidelines.；PSC and non-diseased groups were compared using a two−sided Mann–Whitney U test, with p˂0.05 considered statistically significant.
核心结论
Successful establishment of the PSC model was evidenced by a systemic increase in liver injury markers (AST, ALT, ALP, and T-bil), the histological emergence of representative ductular reactions, and a significant increase in the mHAI score in DDC-fed mice compared with CD-fed mice (Figures A, B).；Under these pathological conditions, we observed a significant upregulation of NQO1 at both the mRNA and protein levels (Figures C, D).；Immunohistochemical analysis further revealed increased NQO1 protein expression in hepatocytes of DDC-fed mice compared with CD-fed mice (Figure E). ‖ 结论：Collectively, our findings indicate that the biological consequences of NQO1 depend on disease stage, substrate availability, and cellular redox context, factors that should be considered when evaluating NQO1 as a potential therapeutic target in cholestatic liver disease.
局限
Certain limitations of the present study warrant consideration.；Finally, in vivo experiments were restricted to male mice, rationalized by the higher incidence of PSC in men and the hepatoprotective nature of estrogen.– However, this choice limits the generalizability of our results.
对本项目的价值
★☆☆☆☆ 线粒体端点既是机制解释层，也是最容易拿到体外 / 影像读数的中间层。
全文来源
PMC JATS 全文（正文 34,790 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：NQO1 acts as a context-dependent regulator of oxidative stress and biliary fibrosis in primary sclerosing cholangitis.
- 期刊与标识：Hepatol Commun · PMID 42951873 · DOI 10.1097/hc9.0000000000001076
A 级证据分级：A 级（同行评议人体研究）
本文属人体研究证据，但需注意：观察性或小样本干预的结论不等于已证实临床获益；效应量与长期安全性仍需更大规模、更长随访的试验验证。
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