DOI: 10.1002/ame2.70128
Establishment of a novel cynomolgus monkey model of hyperuricemia
Ji-Wei Wang1
Le Zhang2
Can Yang2
Guan-Cong Luo2
Rui-Chang Liu2
Yan-Jun Xu2
Sheng Cheng2
Wen-Yu Jiang2
Richard Ward3
Yang Yang2
Cheng Xiang2
Shu An1
Tian-Rui Xu1
1.Department of Pharmaceutical Engineering,Faculty of Life Science and Technology,Kunming University of Science and Technology,Kunming,China;Department of Primate Disease Model Research,State Key Laboratory of Primate Biomedical Research,Kunming University of Science and Technology,Kunming,China;Kunming University of Science and Technology,Kunming,China2.Department of Pharmaceutical Engineering,Faculty of Life Science and Technology,Kunming University of Science and Technology,Kunming,China3.Centre for Translational Pharmacology,Institute of Molecular Cell and Systems Biology,College of Medicine,University of Glasgow,Glasgow,UK
摘要：Background:Chronic hyperuricemia is associated with complications such as gout and uric acid nephropathy,but uric acid also exhibits biological activities(e.g.,antioxidant effects,potential neuroprotective properties against neurodegenerative diseases).Nonhuman primates are ideal models for studying neurodegenerative diseases;how-ever,existing nonhuman primate hyperuricemia models cannot sustain long-term elevated serum uric acid levels,nor recapitulate the impaired uric acid excretion ob-served in clinical hyperuricemic patients.
Methods:First,we detected uricase expression in cynomolgus monkeys and com-pared it with that in mice.Then,we established a cynomolgus monkey hyperurice-mia model by administering a mixture of potassium oxonate,hydrochlorothiazide,and adenine via fruits and vegetables.We further analyzed the regulatory effects of this model on uric acid metabolism(synthesis,degradation,and excretion)and the expres-sion of uric acid transporter genes in the intestine and kidney.
Results:Cynomolgus monkeys express functional uricase,but at a lower level than mice.The established model maintained stable,long-term hyperuricemia by three mechanisms:increasing intestinal and renal uric acid excretion load,inhibiting he-patic uric acid degradation,and promoting uric acid synthesis.Additionally,the model downregulated the expression of intestinal/renal uric acid-secreting transporter genes,while upregulating uric acid-reabsorbing transporter genes.
Conclusions:This novel cynomolgus monkey hyperuricemia model provides a new tool for investigating the association between hyperuricemia and neurodegenerative diseases,and will help clarify the mechanism by which serum uric acid influences cog-nitive function.
机标关键词：novelmodelcynomolgusestablishmenthyperuricemiamonkey
论文发表日期：2026-02-28
在线出版日期：2026-03-31（本平台首次上网日期，不代表文献的发表时间）
页数：13( 354-366 )
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