• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

通过增加β-羟基丁酸（BHB）的产生以及由BHB驱动的信号转导和转录激活因子3（STAT3）信号来促进肝脏再生。

promotes liver regeneration by increasing -hydroxybutyric acid (BHB) production and BHB-driven STAT3 signals.

作者信息

Guo Manlan, Jiang Xiaowen, Ouyang Hui, Zhang Xianglong, Zhang Shuaishuai, Wang Peng, Bi Guofang, Wu Ting, Zhou Wenhong, Liang Fengting, Yang Xiao, Fan Shicheng, Fang Jian-Hong, Chen Peng, Bi Huichang

机构信息

NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.

Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.

出版信息

Acta Pharm Sin B. 2025 Mar;15(3):1430-1446. doi: 10.1016/j.apsb.2025.01.024. Epub 2025 Feb 10.

DOI:10.1016/j.apsb.2025.01.024
PMID:40370533
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12069244/
Abstract

The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of () post-PHx, correlating with hepatocyte proliferation. Treatment with live significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between and -hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both and . Mechanistically, upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering and BHB as potential strategies for promoting hepatic regeneration.

摘要

肝脏再生能力对于接受部分肝切除术（PHx）的终末期肝病患者至关重要。PHx后调节肝脏再生的特定细菌和机制仍不清楚。本研究证明了PHx后（）丰度的动态变化，与肝细胞增殖相关。用活的（）治疗显著促进了PHx后肝细胞增殖和肝脏再生。靶向代谢组学揭示了PHx后肠道中（）与β-羟基丁酸（BHB）以及猪去氧胆酸和3-羟基苯乙酸之间存在显著正相关。值得注意的是，用BHB治疗而非猪去氧胆酸或3-羟基苯乙酸治疗，显著促进了PHx后小鼠的肝细胞增殖和肝脏再生。此外，STAT3抑制剂Stattic在体内和体外均减弱了BHB对细胞增殖和肝脏再生的促进作用。机制上，（）上调了脂肪酸氧化相关蛋白的表达，并增加了肝脏中BHB的水平，然后BHB激活STAT3信号通路以促进肝脏再生。本研究首次确定了（）及其相关代谢物BHB参与促进PHx后的肝脏再生，为将（）和BHB视为促进肝脏再生的潜在策略提供了新见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/42ff708c3b36/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/b3eaf3b50fd9/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/a748fff70106/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/9c44f91f0cf1/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/1ef8ef979d3d/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/08f028366337/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/0eab36c5df87/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/2c596635337d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/2d76f419b127/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/42ff708c3b36/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/b3eaf3b50fd9/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/a748fff70106/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/9c44f91f0cf1/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/1ef8ef979d3d/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/08f028366337/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/0eab36c5df87/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/2c596635337d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/2d76f419b127/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59da/12069244/42ff708c3b36/gr8.jpg

相似文献

1
promotes liver regeneration by increasing -hydroxybutyric acid (BHB) production and BHB-driven STAT3 signals.通过增加β-羟基丁酸（BHB）的产生以及由BHB驱动的信号转导和转录激活因子3（STAT3）信号来促进肝脏再生。
Acta Pharm Sin B. 2025 Mar;15(3):1430-1446. doi: 10.1016/j.apsb.2025.01.024. Epub 2025 Feb 10.
2
Myeloid peroxisome proliferator-activated receptor α deficiency accelerates liver regeneration via IL-6/STAT3 pathway after 2/3 partial hepatectomy in mice.在小鼠2/3部分肝切除术后，髓样过氧化物酶体增殖物激活受体α缺乏通过IL-6/STAT3途径加速肝脏再生。
Hepatobiliary Surg Nutr. 2022 Apr;11(2):199-211. doi: 10.21037/hbsn-20-688.
3
Reticulon 4B (Nogo-B) facilitates hepatocyte proliferation and liver regeneration in mice.Reticulon 4B (Nogo-B) 促进小鼠肝细胞增殖和肝再生。
Hepatology. 2013 May;57(5):1992-2003. doi: 10.1002/hep.26235. Epub 2013 Mar 19.
4
Toll-like receptor 5-mediated signaling enhances liver regeneration in mice.Toll样受体5介导的信号传导增强小鼠肝脏再生。
Mil Med Res. 2021 Feb 23;8(1):16. doi: 10.1186/s40779-021-00309-4.
5
Role of HNF4alpha-cMyc interaction in liver regeneration after partial hepatectomy.HNF4alpha-cMyc 相互作用在部分肝切除术后肝再生中的作用。
Front Endocrinol (Lausanne). 2024 Jul 31;15:1404318. doi: 10.3389/fendo.2024.1404318. eCollection 2024.
6
2,3,5,4'-tetrahydroxy-stilbene-2-O-β-D-glucoside promotes liver regeneration after partial hepatectomy in mice: The potential involvement of PPARα-mediated fatty acid metabolism.2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷促进小鼠肝部分切除术后肝再生：可能涉及 PPARα 介导的脂肪酸代谢。
J Ethnopharmacol. 2024 Nov 15;334:118513. doi: 10.1016/j.jep.2024.118513. Epub 2024 Jul 4.
7
Impact of Gut Recolonization on Liver Regeneration: Hepatic Matrisome Gene Expression after Partial Hepatectomy in Mice.肠道再定植对肝脏再生的影响：小鼠肝部分切除术后肝基质细胞基因表达。
Int J Mol Sci. 2023 Jun 28;24(13):10774. doi: 10.3390/ijms241310774.
8
Deficiency of apoptosis-stimulating protein two of p53 promotes liver regeneration in mice by activating mammalian target of rapamycin.p53 凋亡刺激蛋白 2 的缺乏通过激活哺乳动物雷帕霉素靶蛋白促进小鼠的肝脏再生。
Sci Rep. 2018 Dec 18;8(1):17927. doi: 10.1038/s41598-018-36208-3.
9
Hepatocyte Peroxisome Proliferator-Activated Receptor α Enhances Liver Regeneration after Partial Hepatectomy in Mice.肝细胞过氧化物酶体增殖物激活受体 α 增强小鼠肝部分切除术后的肝再生。
Am J Pathol. 2019 Feb;189(2):272-282. doi: 10.1016/j.ajpath.2018.10.009. Epub 2018 Nov 16.
10
Hepatic vagotomy blunts liver regeneration after hepatectomy by downregulating the expression of interleukin-22.肝迷走神经切断术通过下调白细胞介素-22的表达来抑制肝切除术后的肝脏再生。
World J Gastrointest Surg. 2023 Dec 27;15(12):2866-2878. doi: 10.4240/wjgs.v15.i12.2866.

引用本文的文献

1
Association between the dietary index for gut microbiota and all-cause/cardiovascular mortality in patients with metabolic dysfunction-associated steatotic liver disease.肠道微生物群饮食指数与代谢功能障碍相关脂肪性肝病患者全因/心血管死亡率之间的关联
Diabetol Metab Syndr. 2025 Jul 11;17(1):263. doi: 10.1186/s13098-025-01846-x.
2
Gut microbiota in non-alcoholic fatty liver disease: Pathophysiology, diagnosis, and therapeutics.非酒精性脂肪性肝病中的肠道微生物群：病理生理学、诊断与治疗
World J Hepatol. 2025 Jun 27;17(6):106849. doi: 10.4254/wjh.v17.i6.106849.

本文引用的文献

1
Dietary fiber alleviates alcoholic liver injury via Bacteroides acidifaciens and subsequent ammonia detoxification.膳食纤维通过产丁酸菌和随后的氨解毒缓解酒精性肝损伤。
Cell Host Microbe. 2024 Aug 14;32(8):1331-1346.e6. doi: 10.1016/j.chom.2024.06.008. Epub 2024 Jul 2.
2
Gut Microbiota-Derived 3-Hydroxybutyrate Blocks GPR43-Mediated IL6 Signaling to Ameliorate Radiation Proctopathy.肠道微生物衍生的 3-羟基丁酸通过阻断 GPR43 介导的 IL6 信号转导来改善放射性直肠炎。
Adv Sci (Weinh). 2024 Jul;11(28):e2306217. doi: 10.1002/advs.202306217. Epub 2024 May 14.
3
alleviates diet-induced metabolic dysfunction-associated steatotic liver disease progression by downregulating histone acetylation level via 3-HPAA.
通过3 - HPAA下调组蛋白乙酰化水平，减轻饮食诱导的代谢功能障碍相关脂肪性肝病的进展。
Gut Microbes. 2024 Jan-Dec;16(1):2309683. doi: 10.1080/19490976.2024.2309683. Epub 2024 Feb 5.
4
Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis.熊去氧胆酸通过调节肠-肝轴缓解非酒精性脂肪性肝病。
Cell Metab. 2023 Oct 3;35(10):1752-1766.e8. doi: 10.1016/j.cmet.2023.07.011. Epub 2023 Aug 16.
5
Low Glucose plus β-Hydroxybutyrate Induces an Enhanced Inflammatory Response in Yak Alveolar Macrophages via Activating the GPR109A/NF-κB Signaling Pathway.低血糖联合β-羟丁酸通过激活 GPR109A/NF-κB 信号通路诱导牦牛肺泡巨噬细胞增强的炎症反应。
Int J Mol Sci. 2023 Jul 11;24(14):11331. doi: 10.3390/ijms241411331.
6
Parabacteroides distasonis uses dietary inulin to suppress NASH via its metabolite pentadecanoic acid.副拟杆菌通过其代谢产物十五烷酸利用膳食菊粉来抑制 NASH。
Nat Microbiol. 2023 Aug;8(8):1534-1548. doi: 10.1038/s41564-023-01418-7. Epub 2023 Jun 29.
7
Elevated serum β-hydroxybutyrate, a circulating ketone metabolite, accelerates colorectal cancer proliferation and metastasis via ACAT1.血清β-羟丁酸水平升高，一种循环酮体代谢物，通过 ACAT1 加速结直肠癌的增殖和转移。
Oncogene. 2023 Jun;42(23):1889-1899. doi: 10.1038/s41388-023-02700-y. Epub 2023 Apr 25.
8
YAP regulates the liver size during the fasting-refeeding transition in mice.YAP在小鼠禁食-再喂食转变过程中调节肝脏大小。
Acta Pharm Sin B. 2023 Apr;13(4):1588-1599. doi: 10.1016/j.apsb.2022.12.011. Epub 2022 Dec 21.
9
Parabacteroides distasonis ameliorates hepatic fibrosis potentially via modulating intestinal bile acid metabolism and hepatocyte pyroptosis in male mice.拟杆菌属缓解肝纤维化的作用可能是通过调节雄性小鼠肠道胆汁酸代谢和肝细胞焦亡实现的。
Nat Commun. 2023 Apr 1;14(1):1829. doi: 10.1038/s41467-023-37459-z.
10
Gut microbiota promote liver regeneration through hepatic membrane phospholipid biosynthesis.肠道微生物群通过肝脏膜磷脂生物合成促进肝脏再生。
J Hepatol. 2023 Apr;78(4):820-835. doi: 10.1016/j.jhep.2022.12.028. Epub 2023 Jan 18.