短链脂肪酸对肝纤维化的保护作用及其机制在胰腺纤维化中的类推应用

颜运君; 盛亮; 王祺; 彭顺; 李佳; 张磊

doi:10.12449/JCH260523

短链脂肪酸对肝纤维化的保护作用及其机制在胰腺纤维化中的类推应用

DOI: 10.12449/JCH260523

颜运君^{1, 2, 3},
盛亮^{1, 2, 3, 4, 5},
王祺^{1, 2, 3},
彭顺^{1, 2, 3},
李佳^{1, 2, 3},
张磊^{1, 2, 3, 4, 5, , ,}

1.
兰州大学第一临床医学院，兰州 730000
2.
兰州大学第一医院普外科，兰州 730000
3.
甘肃省生物治疗与再生医学重点实验室，兰州 730000
4.
兰州大学第一医院普通外科国家临床重点专科，兰州 730000
5.
甘肃省普通外科临床医学研究中心，兰州 730000

基金项目:

甘肃省科技重大专项计划项目 (24ZDFA005);

甘肃省卫生行业优秀青年人才和骨干人才项目 (GSWSQN2023-01)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：颜运君负责设计论文框架，起草论文；盛亮和王祺负责查找资料、绘制机制图；彭顺和李佳负责拟定写作思路；张磊指导撰写文章并最后定稿。

详细信息

通信作者:
张磊， ldyy_lzhang@lzu.edu.cn （ORCID： 0009-0009-5562-2951）

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出版历程
- 收稿日期: 2025-09-17
- 录用日期: 2025-10-29
- 出版日期: 2026-05-20

Protective effect of short-chain fatty acids against liver fibrosis and analogical application of its mechanism to pancreatic fibrosis

Yunjun YAN^{1, 2, 3},
Liang SHENG^{1, 2, 3, 4, 5},
Qi WANG^{1, 2, 3},
Shun PENG^{1, 2, 3},
Jia LI^{1, 2, 3},
Lei ZHANG^{1, 2, 3, 4, 5
, ,
,}

1.
The First Clinical Medical School of Lanzhou University，Lanzhou 730000，China
2.
Department of General Surgery，The First Hospital of Lanzhou University，Lanzhou 730000，China
3.
Gansu Province Key Laboratory of Biotherapy and Regenerative Medicine，Lanzhou 730000，China
4.
National Clinical Key Specialty of General Surgery，The First Hospital of Lanzhou University，Lanzhou 730000，China
5.
Gansu Clinical Research Center for General Surgery，The First Hospital of Lanzhou University，Lanzhou 730000，China

Research funding:

Gansu Province Science and Technology Major Special Plan Project (24ZDFA005);

Outstanding Young Talents and Key Talents in Health Industry in Gansu Province (GSWSQN2023-01)

More Information

Corresponding author: ZHANG Lei， ldyy_lzhang@lzu.edu.cn （ORCID： 0009-0009-5562-2951）

摘要

摘要: 短链脂肪酸（SCFA）是膳食纤维经肠道微生物发酵产生的主要代谢产物。研究表明，SCFA不仅在能量代谢中发挥作用，更可作为重要信号分子，在缓解肝及胰腺纤维化进程中展现出显著潜力。其核心机制主要涉及：通过激活G蛋白偶联受体和抑制组蛋白去乙酰化酶活性，调控多种关键信号通路，从而抑制肝星状细胞（HSC）和胰腺星状细胞（PSC）的活化与增殖，干预纤维化形成的核心环节。同时，SCFA能有效减轻组织炎症反应、改善肠道屏障功能、调节肠道菌群平衡，间接阻止“肠-肝/胰轴”介导的纤维化进程。相较于SCFA在肝纤维化中的研究，其在胰腺纤维化中的研究较少。考虑到HSC及PSC高度同源，已在肝纤维化相关研究中证实的转录因子及蛋白在PSC中同样表达，提示其可能同样影响PSC活化。本综述系统梳理了近年SCFA在缓解肝纤维化及胰腺纤维化中的研究进展，旨在为胰腺纤维化的机制探索与干预策略提供新的思路。
- 肝纤维化 /
- 脂肪酸类 /
- 肝星状细胞
Abstract: Short-chain fatty acids （SCFA） are the main metabolic products generated by the fermentation of dietary fiber by gut microbiota. Studies have shown that SCFA not only play a role in energy metabolism， but also act as important signaling molecules， exhibiting a significant potential in alleviating liver and pancreatic fibrosis. The core mechanism of SCFA mainly involves the regulation of various key signaling pathways by activating G protein-coupled receptors and inhibiting the activity of histone deacetylase， thereby suppressing the activation and proliferation of hepatic stellate cell （HSC） and pancreatic stellate cell （PSC）， which is a key link in fibrosis formation. In addition， SCFA can effectively alleviate tissue inflammation response， improve intestinal barrier function， and regulate gut microbiota balance， thus indirectly preventing the process of fibrosis mediated by the “gut-liver/pancreas axis”. Compared with the research on SCFA in liver fibrosis， studies on their role in pancreatic fibrosis are limited. Given that HSC and PSC are highly homologous， the transcription factors and proteins that have been confirmed in liver fibrosis-related studies are also similarly expressed in PSC， suggesting that they may also influence the activation of PSC. This article systematically summarizes the recent advances in the research on SCFA in alleviating liver and pancreatic fibrosis， in order to provide new perspectives for exploring the mechanism of pancreatic fibrosis and developing related interventional strategies.
- Liver Fibrosis /
- Fatty Acids /
- Hepatic Stellate Cells

HTML全文

注： SCFA，短链脂肪酸；LPS，脂多糖；α-SMA，平滑肌肌动蛋白α；HSC，肝星状细胞；HDAC，组蛋白去乙酰化酶；IL-6，白细胞介素6；IL-10，白细胞介素10；TNF-α，肿瘤坏死因子α；TGF-β，转化生长因子β；Treg细胞，调节性T细胞；TLR4，Toll样受体4；Smad，母系抗十五表态蛋白同源物；IRAK1，白细胞介素1受体相关激酶1；ECM，细胞外基质；FXR，法尼醇X受体；FGF15/19，成纤维生长因子15/19；CYP7A1，细胞色素P450家族7亚家族A成员1；NLRP3，核苷酸结合寡聚结构域样受体家族热蛋白结构域相关蛋白3；NF-κB，核因子κB。

图 1 肠道菌群代谢产物SCFA在缓解肝纤维化中的机制

Figure 1. Mechanism of intestinal microbiota metabolite SCFA in alleviating liver fibrosis

下载: 全尺寸图片幻灯片

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