Establishment of mouse hyperuricemia model and detection method of serum uric acid in vivo

doi:10.14088/j.cnki.issn0439-8114.2026.07.024

Abstract

Abstract: To establish a stable mouse model of hyperuricemia (HUA), develop a method for in vivo blood uric acid (UA) detection, and evaluate the effects of different modeling approaches on UA metabolism and liver and kidney tissues in mice, healthy male Kunming mice were used to compare various drug administration regimens and determine the optimal HUA modeling method. Serum UA levels were measured using minimally invasive blood sampling, and the analytical method was validated. Histopathological changes in the liver and kidney were assessed by hematoxylin and eosin (HE) staining, and the transcriptional expression levels of URAT1 and OAT1 in renal tissues were examined by RT-qPCR. Results showed that the optimal HUA modeling method was intragastric administration of a yeast extract‑hypoxanthine suspension combined with intraperitoneal injection of potassium oxonate (YE-HX). This method resulted in the highest serum UA level (276.76 μmol/L), which was 1.62-fold higher than that in the control group, and induced typical HUA‑associated inflammatory pathologies in the liver and kidney, without significantly affecting the transcriptional expression of URAT1 or OAT1 in the kidney. A novel in vivo UA detection method was established using minimally invasive tail‑tip blood sampling (15-20 μL). The method achieved a limit of detection of 0.92 μmol/L, a limit of quantification of 1.70 μmol/L, recovery rates ranging from 88.62% to 105.55%, and a relative standard deviation of 9.31%.

Key words: mouse model of hyperuricemia, modeling, blood uric acid detection, microsampling

CLC Number:

R589.7
R-332

YANG Jing-li, RAN Ya-lan, AI Lun-qiang, LIAO Lu-jing, TAN Yan-hong, LUO Jian-qun, WANG Qing-fang, LI Yu, HE Mei-jun. Establishment of mouse hyperuricemia model and detection method of serum uric acid in vivo[J]. HUBEI AGRICULTURAL SCIENCES, 2026, 65(7): 150-156.

References

[1] KANBAY M, JENSEN T, SOLAK Y, et al.Uric acid in metabolic syndrome: From an innocent bystander to a central player[J]. European journal of internal medicine, 2016, 29: 3-8.
[2] DHOUIBI R, AFFES H, BEN SALEM M, et al.Creation of an adequate animal model of hyperuricemia (acute and chronic hyperuricemia); study of its reversibility and its maintenance[J]. Life sciences, 2021, 268: 118998.
[3] CHEN Y E, LI C T, DUAN S N, et al.Curcumin attenuates potassium oxonate-induced hyperuricemia and kidney inflammation in mice[J]. Biomedicine & pharmacotherapy, 2019, 118: 109195.
[4] LIN S M, MENG J, LI F, et al.Ganoderma lucidumpolysaccharide peptide alleviates hyperuricemia by regulating adenosine deaminase and urate transporters[J]. Food & function, 2022, 13(24): 12619-12631.
[5] 陈光亮,张清林,马晓芹,等.酵母致小鼠高尿酸血症模型[J].中国药理学通报,2003,19(4):467-469.
[6] 熊湘明,曲竹秋.大鼠高尿酸血症模型建立[J].天津中医学院学报,2001,20(4):28-29.
[7] 杨桂梅,黄胜华,连希艳,等.大鼠高尿酸血症模型的建立[J].实验动物科学,2011,28(3):25-28.
[8] XU L Q, LIN G S, YU Q X, et al.Anti-hyperuricemic and nephroprotective effects of dihydroberberine in potassium oxonate- and hypoxanthine-induced hyperuricemic mice[J]. Frontiers in pharmacology, 2021, 12: 645879.
[9] 刘杰,李琴,刘先俊,等.果糖与氧嗪酸钾联用建造高尿酸血症大鼠模型[J].基因组学与应用生物学,2018,37(2):667-674.
[10] 周道远,陈敏,刘岩.不同造模剂诱导大鼠高尿酸血症模型的可行性比较[J].中国比较医学杂志,2012,22(10):23-26.
[11] 赵振升,孔涛,周变华,等.鸡高尿酸血症模型的建立及别嘌呤对其的抑制作用[J].中国兽医学报,2014,34(8):1345-1348.
[12] 潘明子,贺玉伟,李海龙,等.Uox基因敲除自发高尿酸血症对小鼠体重、血压及血液生理生化的影响[J].中国比较医学杂志,2019,29(11):71-77.
[13] LU J, HOU X, YUAN X, et al.Knockout of the urate oxidase gene provides a stable mouse model of hyperuricemia associated with metabolic disorders[J]. Kidney international, 2018, 93(1): 69-80.
[14] 卢忠英,郁建平,朱梦琪,等.不同组合造模剂诱导大鼠高尿酸血症模型的比较研究[J].山地农业生物学报,2014,33(5):40-42,67.
[15] 陈莹莹,靳革,张慧,等.探讨高尿酸血症大鼠模型的建立[J].中国保健营养,2016,26(26):336-337.
[16] WANG M X, LIU Y L, YANG Y, et al.Nuciferine restores potassium oxonate-induced hyperuricemia and kidney inflammation in mice[J]. European journal of pharmacology, 2015, 747: 59-70.
[17] LI Y K, LI H Q, WANG R, et al.Protective effect of sodium butyrate on intestinal barrier damage and uric acid reduction in hyperuricemia mice[J].Biomedicine & pharmacotherapy,2023, 161:114568.
[18] 赵泽安. URAT1转运尿酸的分子机制及抑制剂设计和药理学评价[D].广州:南方医科大学,2023.
[19] LI X, YAN Z, TIAN J, et al.Urate transporter URAT1 in hyperuricemia: New insights from hyperuricemic models[J]. Annals of clinical and laboratory science, 2019,49(6):756-762.
[20] 江民川,赵阳,马芳芳,等.尿酸检测方法的研究进展[J].化工科技,2021,29(3):75-79.
[21] 杨莉,谭唱,王莉,等.最新血尿酸检测方法概述[J].吉林医学,2014,35(1):144-145.