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更新于：2025-05-07

CYP8B1

更新于：2025-05-07

基本信息

别名

7-alpha-hydroxy-4-cholesten-3-one 12-alpha-hydroxylase、7-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylase、CYP12

+ [7]

简介

A cytochrome P450 monooxygenase involved in primary bile acid biosynthesis. Catalyzes the 12alpha-hydroxylation of 7alpha-hydroxy-4-cholesten-3-one, an intermediate metabolite in cholic acid biosynthesis (PubMed:10051404). Controls biliary balance of cholic acid and chenodeoxycholic acid, ultimately regulating the intestinal absorption of dietary lipids (By similarity). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH--hemoprotein reductase) (By similarity).

关联

100 项与 CYP8B1 相关的临床结果

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100 项与 CYP8B1 相关的转化医学

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0 项与 CYP8B1 相关的专利（医药）

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381

项与 CYP8B1 相关的文献（医药）

2025-05-01·Molecular Metabolism

Glucagon-like peptide-2 pharmacotherapy activates hepatic Farnesoid X receptor-signaling to attenuate resection-associated bile acid loss in mice

Article

作者: Berlin, Peggy ; Witte, Maria ; Jaster, Robert ; Adamski, Jerzy ; Krause, Bernd J ; Reiner, Johannes ; Prehn, Cornelia ; Lamprecht, Georg ; Förster, Robert H ; Mohebali, Nooshin ; Elleisy, Nagi ; Vollmar, Brigitte ; Kurth, Jens ; Schwarzenböck, Sarah M ; Lindner, Tobias ; Cecil, Alexander

OBJECTIVEVillus growth in the small bowel by Glucagon-like peptide-2 (GLP-2) pharmacotherapy improves intestinal absorption capacity and is now used clinically for the treatment of short bowel syndrome and intestinal failure occurring after extensive intestinal resection. Another recently acknowledged effect of GLP-2 treatment is the inhibition of gallbladder motility and increased gallbladder refilling. However, the impact of these two GLP-2-characteristic effects on bile acid metabolism in health and after intestinal resection is not understood.METHODSMice were injected with the GLP-2-analogue teduglutide or vehicle. We combined the selenium-75-homocholic acid taurine (SeHCAT) assay with novel spatial imaging in healthy mice and after ileocecal resection (ICR mice) and associated the results with clinical stage targeted bile acid metabolomics as well as gene expression analyses.RESULTSICR mice had virtual complete intestinal loss of secondary bile acids, and an increased ratio of 12α-hydroxylated vs. non-12α-hydroxylated bile acids, which was attenuated by teduglutide. Teduglutide promoted SeHCAT retention in healthy and in ICR mice. Acute concentration of the SeHCAT-signal into the hepatobiliary system was observed. Teduglutide induced significant repression of hepatic cyp8b1 expression, likely by induction of MAF BZIP Transcription Factor G.CONCLUSIONSThe data suggest that GLP-2-pharmacotherapy in mice significantly slows bile acid circulation primarily via hepatic Farnesoid X receptor-signaling.

2025-04-01·Ecotoxicology and Environmental Safety

Destruction of the intestinal microbiota and gut–liver axis homeostasis by microcystin-LR-induced inflammation in the common carp (Cyprinus carpio)

Article

作者: Gao, Zhaolu ; Yang, Yanzhe ; Ding, Cuihong ; Li, Xiaoyu ; Ding, Weikai ; Ma, Junguo

Water eutrophication leads to the frequent occurrence of cyanobacterial blooms, which pose a serious threat to the health and survival of fish, the top consumer in freshwater ecosystems. The hepatotoxicity induced by microcystin-LR (MC-LR) has been well studied; however, its impact on the intestinal flora and the gut-liver axis has rarely been reported. This study aimed to investigate the harmful effects of acute oral (303.89 µg/kg.bw) and intraperitoneal (i.p., 101.3 µg/kg.bw) exposure to MC-LR on the intestine and liver and the gut-liver axis of common carp. The results showed that the transaminase activity and levels of proinflammatory factors increased significantly, and histological abnormalities were observed, indicating that MC-LR induced a hepatoenteric inflammatory response. The levels of gram-negative bacteria increased, but the expression levels of bile acid (BA)-related genes (cyp7a1, cyp8b1, cyp27a1, and fxr) and the short-chain fatty acid (SCFA) content decreased as the LPS level increased. These results suggest that MC-LR exposure induces liver inflammation and impairs BA synthesis, weakening intestinal defences and promoting LPS-related hepatic inflammation. Additionally, increased intestinal permeability and reduced SCFA synthesis can further compromise intestinal epithelium protection. The inflammation induced by MC-LR was significantly more severe in the liver than in the intestine, and the recovery of the liver was slower. This study enhances the understanding of the environmental risks posed by cyanobacteria.

2025-04-01·Toxicology and Applied Pharmacology

Hepatotoxicity from long-term administration of hepatoprotective low doses of oleanolic acid in mice

Article

作者: Liu, Jie ; Yang, Xi ; Xu, Yasha ; Lu, Yuanfu

Oleanolic acid is a triterpenoid existed in many medicinal herbs/plants. Oleanolic acid at low doses are hepatoprotective but at high doses produce cholestasis. This study examined hepatotoxicity potential of low doses of oleanolic acid after log-term administration. Male Kunming mice were orally given oleanolic acid at 100, 200 and 300 μmol/kg daily for 14 weeks. Body weights were monitored, and liver injury was determined via blood biochemistry. Histopathology was examined via H&E, Masson, and Sirius red stains. Oleanolic acid accumulation in plasma and liver was determined by LC-MS and hepatic gene expression by qPCR. Oleanolic acid at low doses did not affect animal body weights, but increased liver index. Serum alanine aminotransferase and alkaline phosphatase were increased, while total bilirubin was unchanged. Chronic oleanolic acid produced hepatocyte degeneration, spot necrosis, and fibrosis. Plasma oleanolic acid was increased more than that in the liver. Oleanolic acid increased hepatic expression of Nrf2, Nqo1, Gclc and Mgst1; Expression of bile acid synthesis genes (Cyp7a1, Cyp8b1, Cyp27a1, Cyp7b1, FXR, SHP) was also suppressed at higher doses. The expression of TGF-β1 and Smad3 was increased, while Smad7 decreased, suggesting the progression to liver fibrosis. High dose of oleanolic acid was less effective in producing these changes, probably due to increased liver injury. Overall, oral administration of low doses of oleanolic acid for 14 weeks produced liver injury and fibrosis. These harmful effects were associated with increased oleanolic acid in plasma and liver, and the disruptions of bile acid metabolism, the Nrf2 and TGF-β/Smad signaling pathways.

项与 CYP8B1 相关的新闻（医药）

2022-09-09

·生物谷

Cell Stem Cell：发现肝脏胆汁酸代谢影响肠道屏障功能分子机制

肠上皮屏障损伤在炎症性肠病（IBD）细胞和分子发病机制研究中备受关注。肠上皮屏障结构和功能的完整性依赖稳定更新的上皮细胞和具有正常功能的细胞旁通路。胆汁酸是肝脏中胆固醇分解的最终产物，主要通过法尼肠上皮屏障损伤在炎症性肠病（IBD）细胞和分子发病机制研究中备受关注。肠上皮屏障结构和功能的完整性依赖稳定更新的上皮细胞和具有正常功能的细胞旁通路。胆汁酸是肝脏中胆固醇分解的最终产物，主要通过法尼醇X受体（FXR）和G蛋白偶联胆汁酸受体1（TGR5）调节机体能量代谢和免疫功能等。已有研究表明，胆汁酸是肠上皮屏障功能的重要调控物质，但内在机制尚不清晰。中国科学院上海药物研究所、上海中医药大学龙华医院与美国国立卫生研究院合作，在肠道上皮屏障修复的跨器官调控机制研究中取得重要进展。相关研究成果以Hepatic cytochrome P450 8B1 and cholic acid potentiate intestinal epithelial injury in colitis by suppressing intestinal stem cell renewal为题，在线发表在Cell Stem Cell上。研究发现，活动期IBD患者和结肠炎小鼠体内胆汁酸代谢紊乱，胆酸（CA）水平显著上调，且肝脏胆汁酸经典合成途径代谢酶CYP8B1出现过度活化。外源补充CA或过表达CYP8B1均能够加重小鼠IBD表型、损伤肠道屏障及其修复功能，而干扰CYP8B1的表达则可促进肠道炎症缓解，恢复肠上皮再生能力。　　隐窝肠道干细胞（Lgr5+ ISC）的自我更新在维持肠稳态、抵御微生物入侵中发挥重要作用。为剖析CYP8B1-CA代谢轴影响肠干细胞（ISC）更新的机制，研究分离结肠炎小鼠的肠道隐窝和ISC进行体外培养，发现病理浓度的CA显著减弱结肠炎小鼠隐窝中类器官的出芽和传代能力，并直接抑制Lgr5+ ISC的增殖（图1）。　　进一步的RNA-Seq和代谢组学分析中发现，CA可抑制结肠炎小鼠隐窝的脂肪酸氧化（FAO）过程及PPARα信号通路。研究通过肠特异性敲除Pparα的结肠炎小鼠证实了CYP8B1-CA代谢轴通过抑制PPARα介导的FAO，削弱Lgr5+ ISC的更新能力，加重肠道屏障损伤。研究应用FXR激动剂奥贝胆酸（OCA）间接抑制结肠炎小鼠体内CYP8B1的活性，可促进其Lgr5+ ISC的增殖和传代能力，验证了肝脏FXR-CYP8B1-CA代谢轴在IBD中的重要作用。图1.CA直接抑制Lgr5+ ISC的增殖　　该研究发现在炎症性肠病状态下，CYP8B1异常活化并导致其产物CA积累，远程抑制隐窝基底部ISC的自我更新，阻止肠上皮屏障修复。该研究提出了肝脏FXR和CYP8B1有望成为“肠病肝治”的新靶标，并发现了FXR激动剂能够兼顾调节炎症和修复受损的肠上皮屏障，因而FXR的激动剂有望成为更有前景的IBD治疗药物。。　　研究工作得到国家重点研发计划、中科院战略性先导科技专项（B类）、上海市科技重大专项和国家自然科学基金等的资助，并获得中科院上海营养与健康研究所、上海交通大学精准医学研究院的科研人员的支持。

2022-09-05

·中国生物技术网

新研究发现肝脏胆汁酸代谢影响肠道屏障功能的分子机制

肠上皮屏障损伤在炎症性肠病（IBD）细胞和分子发病机制研究中备受关注。肠上皮屏障结构和功能的完整性依赖于稳定更新的上皮细胞和具有正常功能的细胞旁通路。胆汁酸是肝脏中胆固醇分解的最终产物，主要通过法尼醇X受体（FXR）和G 蛋白偶联胆汁酸受体1（TGR5）调节机体能量代谢和免疫功能等。已有研究表明，胆汁酸是肠上皮屏障功能的重要调控物质，但其内在机制尚未阐明。2022年9月1日，发表在《Cell Stem Cell》上的一项最新研究中，来自中国科学院上海药物研究所、上海中医药大学龙华医院与美国国立卫生研究院联合团队在肠道上皮屏障修复的跨器官调控机制研究中获得重要发现。研究人员发现活动期IBD患者和结肠炎小鼠体内胆汁酸代谢紊乱，胆酸（CA）水平显著上调，且肝脏胆汁酸经典合成途径代谢酶CYP8B1出现过度活化。通过外源补充CA或过表达CYP8B1均能够加重小鼠IBD表型，损伤肠道屏障及其修复功能，而干扰CYP8B1的表达则可促进肠道炎症缓解，恢复肠上皮再生能力。隐窝肠道干细胞（Lgr5+ ISC）的自我更新在维持肠稳态、抵御微生物入侵中发挥重要作用。为深入了解CYP8B1-CA代谢轴影响肠干细胞（ISC）更新的机制，研究人员分离结肠炎小鼠的肠道隐窝和ISC进行体外培养，发现病理浓度的CA显著减弱结肠炎小鼠隐窝中类器官的出芽和传代能力，并直接抑制Lgr5+ ISC的增殖（图1）。图1. CA直接抑制Lgr5+ ISC的增殖在进一步的RNA-Seq和代谢组学分析中，研究人员发现CA可抑制结肠炎小鼠隐窝的脂肪酸氧化（FAO）过程及PPARα信号通路。他们通过肠特异性敲除Pparα的结肠炎小鼠证实了CYP8B1-CA代谢轴通过抑制PPARα介导的FAO，削弱Lgr5+ ISC的更新能力，加重肠道屏障损伤。最后，研究人员应用FXR激动剂奥贝胆酸（OCA）间接抑制结肠炎小鼠体内CYP8B1的活性，能够促进其Lgr5+ ISC的增殖和传代能力，验证了肝脏FXR-CYP8B1-CA代谢轴在IBD中的重要作用。综上，该研究发现在炎症性肠病状态下，CYP8B1异常活化并导致其产物CA积累，远程抑制隐窝基底部ISC的自我更新，阻止肠上皮屏障修复。研究人员不仅提出肝脏FXR和CYP8B1有望成为“肠病肝治”的新靶标，同时也发现FXR激动剂能够兼顾调节炎症和修复受损的肠上皮屏障，因此FXR激动剂有望成为更有前景的IBD治疗药物。（图2）。图2. 肝脏CYP8B1-CA代谢轴跨器官调控肠道上皮损伤修复的分子机制。论文链接：https://www.sciencedirect.com/science/article/pii/S1934590922003447

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