| 于湘宁,周力荧,王海强.成纤维细胞生长因子 19在代谢相关脂肪性肝病中的调控机制及治疗前景[J].安徽医药,2026,30(11):2121-2128. |
| 成纤维细胞生长因子 19在代谢相关脂肪性肝病中的调控机制及治疗前景 |
| Fibroblast growth factor 19 in metabolic-associated fatty liver disease: regulatory mechanisms and therapeutic prospects |
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| DOI：10.3969/j.issn.1009-6469.2026.11.001 |
| 中文关键词: 代谢相关脂肪性肝病 成纤维细胞生长因子 胆汁酸 脂质代谢 肠道菌群 |
| 英文关键词: Non-alcoholic fatty liver disease Fibroblast growth factor Bile acid Lipid metabolism Gut microbiota |
| 基金项目:国家自然科学基金培育支持计划项目( PYMS202501016)；国家中医药管理局第五批全国中医临床优秀人才研修项目(国中医药人教函［2022］1号)；黑龙江省中医药管理局科研项目( ZHY2023-125) |
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| 中文摘要: |
| 代谢相关脂肪性肝病( MAFLD)病理进展主要涉及脂质代谢紊乱、炎症反应及肝纤维化等多重机制。成纤维细胞生长因子 19(FGF19)作为胆汁酸 -代谢 -炎症调控的枢纽角色，通过激活 FGFR4/β-Klotho受体复合物，抑制胆汁酸合成限速酶 CYP7A1，调节脂质代谢，改善胰岛素敏感性，并抑制肝星状细胞活化以及巨噬细胞 M1极化，在 MAFLD中发挥了多层面保护作用。目前相关研究多基于动物模型，对于纤维化阶段的临床疗效尚缺乏大规模样本的验证。现有研究表明工程化 FGF19类似物如 NGM282通过靶向治疗显著提升了其代谢调控能力，然而 FGF19-FGFR4信号通路的长期安全性仍需进一步严谨评估。该综述系统阐述了 FGF19在 MAFLD中的分子机制及治疗潜力，强调其作为代谢 -炎症调控靶点的临床应用前景，并整合了其与肠道菌群轴、表观遗传调控等新兴机制的相关性，展望了未来研究的挑战与转化方向。 |
| 英文摘要: |
| The pathological progression of metabolic-associated fatty liver disease (MAFLD) primarily involves multiple mechanisms,including lipid metabolism disorders, inflammatory responses, and liver fibrosis. As a pivotal hub in the bile acid-metabolism-inflamma-tion regulatory axis, fibroblast growth factor 19 (FGF19) exerts multifaceted protective effects in MAFLD by activating the FGFR4/β -Klotho receptor complex, inhibiting the bile acid synthesis rate-limiting enzyme CYP7A1 to regulate lipid metabolism, improving insu-lin sensitivity, and suppressing hepatic stellate cell activation and macrophage M1 polarization. Current studies are primarily based onanimal models, and clinical efficacy in the fibrosis stageremains to be validated by large-scale cohort studies.Existing evidence indi-cates that engineered FGF19 analogues such as NGM282 significantly enhance metabolic regulation through targeted therapy; however,the long-term safety of the FGF19-FGFR4 signaling pathway still requires further rigorous evaluation. This review systematically eluci-dates the molecular mechanisms and therapeutic potential of FGF19 in MAFLD, emphasizes its clinical application prospects as a met-abolic-inflammatory regulatory target, and integrates its relevance to emerging mechanisms such as the gut microbiota axis and epigene-tic regulation, while outlining future research challenges and translational directions. |
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