Zhang Senyue, Li Kaiqing, Zhang Hu, Fu Tong, Ma Yanchun, Zhang Shuxiang, Xing Guoli, Tong Ying
Heilongjiang University of Chinese Medicine, Harbin, China.
Department of Rheumatology, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, China.
Front Pharmacol. 2025 Aug 22;16:1636205. doi: 10.3389/fphar.2025.1636205. eCollection 2025.
Hyperuricemia (HUA) is a prevalent metabolic disorder driven by dysregulated purine metabolism and impaired urate excretion, and robust animal models are critical for elucidating its pathophysiology and guiding therapy development. This review systematically examines chemically induced, gene-edited, environmental, exercise and microbiota-based HUA models across rodents, poultry, primates, zebrafish and silkworms, highlighting each model's strengths and limitations in mimicking human uric acid handling. We discuss how these models have validated standard urate-lowering treatments-such as xanthine oxidase inhibitors and uricosurics-and uncovered emerging therapeutic targets, including the gut-NLRP3 inflammasome axis and SIRT1-mediated ABCG2 regulation. Finally, we propose a unified three-tier framework encompassing biochemical, mechanistic and pathological criteria to standardize model evaluation and accelerate translational research in hyperuricemia.
高尿酸血症（HUA）是一种由嘌呤代谢失调和尿酸排泄受损驱动的常见代谢紊乱疾病，强大的动物模型对于阐明其病理生理学和指导治疗方法的开发至关重要。本综述系统地研究了基于化学诱导、基因编辑、环境、运动和微生物群的啮齿动物、家禽、灵长类动物、斑马鱼和蚕的高尿酸血症模型，突出了每种模型在模拟人类尿酸处理方面的优势和局限性。我们讨论了这些模型如何验证了标准的降尿酸治疗方法，如黄嘌呤氧化酶抑制剂和促尿酸排泄药，并发现了新出现的治疗靶点，包括肠道-NLRP3炎性小体轴和SIRT1介导的ABCG2调节。最后，我们提出了一个统一的三层框架，涵盖生化、机制和病理标准，以规范模型评估并加速高尿酸血症的转化研究。
