尿酸与MASLD肝纤维化的研究进展
Research Progress on Uric Acid and MASLD-Related Liver Fibrosis
DOI: 10.12677/acm.2025.15103032, PDF,   
作者: 苏帅莹, 章梦成：绍兴文理学院医学院，浙江 绍兴；张明琛*：宁波市第二医院内分泌与代谢科，浙江 宁波
关键词: 尿酸；MASLD；肝纤维化；机制研究；Uric Acid； MASLD； Liver Fibrosis； Mechanistic Studies
摘要: 肝纤维化(Liver fibrosis, LF)是各种慢性肝脏疾病的殊途同归，患病率逐年上升，目前尚缺乏有效的治疗手段。近年来的研究表明，过高的尿酸(uric acid, UA)水平可能是导致肝纤维化的重要因素之一，尤其在代谢功能障碍相关脂肪性肝病(metabolic dysfunction-associated steatotic liver disease，MASLD，以前称为NAFLD)中，UA可能通过多种机制参与肝纤维化的发生发展。本文就UA与MASLD肝纤维化的研究进展进行综述，为临床防治MASLD肝纤维化提供新的思路。
Abstract: Liver fibrosis (LF) is a common pathological outcome of various chronic liver diseases, with its prevalence increasing annually. Currently, there are no effective therapeutic strategies. Recent studies suggest that elevated uric acid (UA) levels may be a significant contributing factor to liver fibrosis, particularly in metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as NAFLD). UA is implicated in the pathogenesis and progression of liver fibrosis through multiple mechanisms. This review summarizes recent advances in understanding the role of UA in MASLD-related liver fibrosis, aiming to provide new insights for clinical prevention and treatment.
文章引用：苏帅莹, 章梦成, 张明琛. 尿酸与MASLD肝纤维化的研究进展[J]. 临床医学进展, 2025, 15(10): 2457-2465. https://doi.org/10.12677/acm.2025.15103032

参考文献

[1] Ginès, P., Castera, L., Lammert, F., Graupera, I., Serra‐Burriel, M., Allen, A.M., et al. (2022) Population Screening for Liver Fibrosis: Toward Early Diagnosis and Intervention for Chronic Liver Diseases. Hepatology, 75, 219-228. [Google Scholar] [CrossRef] [PubMed]
[2] Kisseleva, T. and Brenner, D. (2021) Molecular and Cellular Mechanisms of Liver Fibrosis and Its Regression. Nature Reviews Gastroenterology & Hepatology, 18, 151-166. [Google Scholar] [CrossRef] [PubMed]
[3] 中华医学会肝病学分会. 代谢相关(非酒精性)脂肪性肝病防治指南(2024年版) [J]. 中华肝脏病杂志, 2024, 32(5): 418-434.
[4] Hagström, H., Shang, Y., Hegmar, H. and Nasr, P. (2024) Natural History and Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease. The Lancet Gastroenterology & Hepatology, 9, 944-956. [Google Scholar] [CrossRef] [PubMed]
[5] 中华医学会内分泌学分会. 中国高尿酸血症与痛风诊疗指南(2019) [J]. 中华内分泌代谢杂志, 2020, 36(1): 1-13.
[6] Du, L., Zong, Y., Li, H., Wang, Q., Xie, L., Yang, B., et al. (2024) Hyperuricemia and Its Related Diseases: Mechanisms and Advances in Therapy. Signal Transduction and Targeted Therapy, 9, Article No. 212. [Google Scholar] [CrossRef] [PubMed]
[7] Wen, S., Arakawa, H. and Tamai, I. (2024) Uric Acid in Health and Disease: From Physiological Functions to Pathogenic Mechanisms. Pharmacology & Therapeutics, 256, Article 108615. [Google Scholar] [CrossRef] [PubMed]
[8] 侯淑惠, 邓晓玲, 次白, 等. 尿酸参与代谢相关性脂肪性肝病发生、发展的分子机制研究进展[J]. 肝脏, 2023, 28(8): 990-994.
[9] Mangan, M.S.J., Olhava, E.J., Roush, W.R., Seidel, H.M., Glick, G.D. and Latz, E. (2018) Erratum: Targeting the NLRP3 Inflammasome in Inflammatory Diseases. Nature Reviews Drug Discovery, 17, 688-688. [Google Scholar] [CrossRef] [PubMed]
[10] Wen, L., Yang, H., Ma, L. and Fu, P. (2021) The Roles of NLRP3 Inflammasome-Mediated Signaling Pathways in Hyperuricemic Nephropathy. Molecular and Cellular Biochemistry, 476, 1377-1386. [Google Scholar] [CrossRef] [PubMed]
[11] Dai, C., Fang, T., Hung, W., Tsai, H. and Tsai, Y. (2022) The Determinants of Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus. Biomedicines, 10, Article 1487. [Google Scholar] [CrossRef] [PubMed]
[12] Lee, J.M., Kim, H.W., Heo, S.Y., Do, K.Y., Lee, J.D., Han, S.K., et al. (2023) Associations of Serum Uric Acid Level with Liver Enzymes, Nonalcoholic Fatty Liver Disease, and Liver Fibrosis in Korean Men and Women: A Cross-Sectional Study Using Nationally Representative Data. Journal of Korean Medical Science, 38, e267. [Google Scholar] [CrossRef] [PubMed]
[13] Yu, W., Xie, D., Yamamoto, T., Koyama, H. and Cheng, J. (2023) Mechanistic Insights of Soluble Uric Acid-Induced Insulin Resistance: Insulin Signaling and Beyond. Reviews in Endocrine and Metabolic Disorders, 24, 327-343. [Google Scholar] [CrossRef] [PubMed]
[14] Xie, D., Zhao, H., Lu, J., He, F., Liu, W., Yu, W., et al. (2021) High Uric Acid Induces Liver Fat Accumulation via ROS/JNK/AP-1 Signaling. American Journal of Physiology-Endocrinology and Metabolism, 320, E1032-E1043. [Google Scholar] [CrossRef] [PubMed]
[15] Ashraf, H., Anushiravani, A., Rayatpisheh, M., Hamidi Alamdari, D., Hossieni, A. and Kazeminezhad, B. (2025) Association between Oxidative Stress and Liver Fibrosis Severity in Non-Alcoholic Fatty Liver Disease: Insights from the Pro-Oxidant Antioxidant Balance Method in a Population from Tehran and Mashhad, Iran. Frontiers in Medicine, 12, Article ID: 1539605. [Google Scholar] [CrossRef] [PubMed]
[16] Sun, X., Jiao, H., Zhao, J., Wang, X. and Lin, H. (2017) Unexpected Effect of Urate on Hydrogen Peroxide-Induced Oxidative Damage in Embryonic Chicken Cardiac Cells. Free Radical Research, 51, 693-707. [Google Scholar] [CrossRef] [PubMed]
[17] Zhou, J., Zheng, Q. and Chen, Z. (2022) The Nrf2 Pathway in Liver Diseases. Frontiers in Cell and Developmental Biology, 10, Article ID: 826204. [Google Scholar] [CrossRef] [PubMed]
[18] Mohs, A., Otto, T., Schneider, K.M., Peltzer, M., Boekschoten, M., Holland, C.H., et al. (2021) Hepatocyte-Specific Nrf2 Activation Controls Fibrogenesis and Carcinogenesis in Steatohepatitis. Journal of Hepatology, 74, 638-648. [Google Scholar] [CrossRef] [PubMed]
[19] Yang, S., Zou, Y., Zhong, C., Zhou, Z., Peng, X. and Tang, C. (2025) Dual Role of Pyroptosis in Liver Diseases: Mechanisms, Implications, and Therapeutic Perspectives. Frontiers in Cell and Developmental Biology, 13, Article ID: 1522206. [Google Scholar] [CrossRef] [PubMed]
[20] Xu, Z., Tang, C., Song, X., Liu, Z., Zhou, J., Shi, Q., et al. (2025) High Uric Acid Exacerbates Nonalcoholic Steatohepatitis through NLRP3 Inflammasome and Gasdermin D-Mediated Pyroptosis. Journal of Biological Chemistry, 301, Article 110249. [Google Scholar] [CrossRef] [PubMed]
[21] Wang, T., Xia, G., Li, X., Gong, M. and Lv, X. (2025) Endoplasmic Reticulum Stress in Liver Fibrosis: Mechanisms and Therapeutic Potential. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1871, Article 167695. [Google Scholar] [CrossRef] [PubMed]
[22] Choi, Y., Shin, H., Choi, H.S., Park, J., Jo, I., Oh, E., et al. (2014) Uric Acid Induces Fat Accumulation via Generation of Endoplasmic Reticulum Stress and Srebp-1c Activation in Hepatocytes. Laboratory Investigation, 94, 1114-1125. [Google Scholar] [CrossRef] [PubMed]
[23] Lau, H.C.-H., Zhang, X. and Yu, J. (2025) Gut Microbiome in Metabolic Dysfunction-Associated Steatotic Liver Disease and Associated Hepatocellular Carcinoma. Nature Reviews Gastroenterology & Hepatology, 22, 619-638.
[24] Zhou, X., Ji, S., Chen, L., Liu, X., Deng, Y., You, Y., et al. (2024) Gut Microbiota Dysbiosis in Hyperuricaemia Promotes Renal Injury through the Activation of Nlrp3 Inflammasome. Microbiome, 12, Article No. 109. [Google Scholar] [CrossRef] [PubMed]
[25] Nishikawa, T., Nagata, N., Shimakami, T., Shirakura, T., Matsui, C., Ni, Y., et al. (2020) Xanthine Oxidase Inhibition Attenuates Insulin Resistance and Diet-Induced Steatohepatitis in Mice. Scientific Reports, 10, Article No. 815. [Google Scholar] [CrossRef] [PubMed]
[26] Sari, D.C.R., Soetoko, A.S., Soetoko, A.S., et al. (2020) Uric Acid Induces Liver Fibrosis Through Activation of Inflammatory Mediators and Proliferating Hepatic Stellate Cell in Mice. Medical Journal of Malaysia, 75, 14-18.
[27] Kakimoto, M., Fujii, M., Sato, I., Honma, K., Nakayama, H., Kirihara, S., et al. (2023) Antioxidant Action of Xanthine Oxidase Inhibitor Febuxostat Protects the Liver and Blood Vasculature in SHRSP5/Dmcr Rats. Journal of Applied Biomedicine, 21, 80-90. [Google Scholar] [CrossRef] [PubMed]
[28] Yokose, C., McCormick, N., Abhishek, A., Dalbeth, N., Pascart, T., Lioté, F., et al. (2024) The Clinical Benefits of Sodium-Glucose Cotransporter Type 2 Inhibitors in People with Gout. Nature Reviews Rheumatology, 20, 216-231. [Google Scholar] [CrossRef] [PubMed]
[29] Hirayama, K., Koshizaka, M., Ishibashi, R., Shoji, M., Horikoshi, T., Sakurai, K., et al. (2025) Effects of the SGLT2 Inhibitor Ipragliflozin and Metformin on Hepatic Steatosis and Liver Fibrosis: Sub‐Analysis of a Randomized Controlled Study. Diabetes, Obesity and Metabolism, 27, 2059-2069. [Google Scholar] [CrossRef] [PubMed]
[30] Ji, L., Jiang, H., Bi, Y., Li, H., Tian, J., Liu, D., et al. (2025) Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight. New England Journal of Medicine, 392, 2215-2225. [Google Scholar] [CrossRef] [PubMed]
[31] Tanaka, Y., Nagoshi, T., Takahashi, H., Oi, Y., Yoshii, A., Kimura, H., et al. (2022) Urat1-Selective Inhibition Ameliorates Insulin Resistance by Attenuating Diet-Induced Hepatic Steatosis and Brown Adipose Tissue Whitening in Mice. Molecular Metabolism, 55, Article 101411. [Google Scholar] [CrossRef] [PubMed]
[32] Matsushita, D., Toyoda, Y., Lee, Y., Aoi, M., Matsuo, H., Takada, T., et al. (2025) Structural Basis of Urate Transport by Glucose Transporter 9. Cell Reports, 44, Article 115514. [Google Scholar] [CrossRef] [PubMed]
[33] Shen, Z., Xu, L., Wu, T., Wang, H., Wang, Q., Ge, X., et al. (2024) Structural Basis for Urate Recognition and Apigenin Inhibition of Human Glut9. Nature Communications, 15, Article No. 5039. [Google Scholar] [CrossRef] [PubMed]
[34] Hsu, M., Guo, B., Chen, C., Hu, P., Chen, W. and Lee, T. (2025) Rac1 Signaling Mediates the Protection of Apigenin against Hepatic Lipid Accumulation and Insulin Resistance. Biomedicine & Pharmacotherapy, 189, Article 118265. [Google Scholar] [CrossRef] [PubMed]

为你推荐