Establishment and Evaluation of Hyperuricemia Mouse Model with Damp-Turbidity Internal Accumulation Syndrome

ZHANG Yue; LI Xiangyu; YANG Xuan; WANG Shenzhi; FAN Xinrong

doi:10.13288/j.11-2166/r.2026.14.012

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Establishment and Evaluation of Hyperuricemia Mouse Model with Damp-Turbidity Internal Accumulation Syndrome

更新时间：2026-07-17

- Establishment and Evaluation of Hyperuricemia Mouse Model with Damp-Turbidity Internal Accumulation Syndrome
- Journal of Traditional Chinese Medicine Vol. 67, Issue 14, Pages: 1538-1545(2026)
- 作者机构：
  
  1.中国中医科学院医学实验中心，北京市东城区东直门内南小街16号，100700
  2.湖南中医药大学第一附属医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2026.14.012
  CLC：
- Received：08 January 2026，
  
  Revised：2026-03-12，
  
  Accepted：14 February 2026，
  
  Online First：15 July 2026，
  
  Published：17 July 2026
- 稿件说明：
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张悦,李翔宇,杨璇等.高尿酸血症湿浊内蕴证小鼠模型的构建与评价[J].中医杂志,2026,67(14):1538-1545.

ZHANG Yue,LI Xiangyu,YANG Xuan,et al.Establishment and Evaluation of Hyperuricemia Mouse Model with Damp-Turbidity Internal Accumulation Syndrome[J].Journal of Traditional Chinese Medicine,2026,67(14):1538-1545.
张悦,李翔宇,杨璇等.高尿酸血症湿浊内蕴证小鼠模型的构建与评价[J].中医杂志,2026,67(14):1538-1545. DOI： 10.13288/j.11-2166/r.2026.14.012.

ZHANG Yue,LI Xiangyu,YANG Xuan,et al.Establishment and Evaluation of Hyperuricemia Mouse Model with Damp-Turbidity Internal Accumulation Syndrome[J].Journal of Traditional Chinese Medicine,2026,67(14):1538-1545. DOI： 10.13288/j.11-2166/r.2026.14.012.

摘要

目的

构建符合中医湿浊内蕴证特点的高尿酸血症（HUA）小鼠模型，并对其进行评价。

方法

36只C57BL/6J小鼠随机分为空白组、化模组、化模高脂劳倦组，24只尿酸氧化酶基因敲除（UOX

-/-

）小鼠随机分为UOX

-/-

组和UOX

-/-

高脂劳倦组，每组12只。化模组和化模高脂劳倦组采用氧嗪酸钾联合腺嘌呤灌胃构建HUA模型；化模高脂劳倦组和UOX

-/-

高脂劳倦组采用高脂饲料结合负重力竭游泳构建HUA湿浊内蕴证模型。于造模第1、7、14、21、28天观察各组小鼠湿浊内蕴证候积分；造模第1、28天进行负重力竭游泳实验，记录负重力竭游泳时间；造模第28天，计算肝脏、肾脏指数，采用HE染色法观察肝脏、肾脏病理损伤形态，采用生化法检测血清尿酸（UA）、黄嘌呤脱氢酶（XDH）、黄嘌呤氧化酶（XOD）和尿素氮（BUN）水平，采用ELISA法检测血清肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）水平，采用免疫组化法检测肾脏组织有机阴离子转运蛋白1（OAT1）和葡萄糖转运体（GLUT9）蛋白表达，采用实时荧光定量PCR法检测肾脏组织三磷酸腺苷结合转运蛋白G2（

ABCG2

）、缺氧诱导因子-1α（

HIF

1α

）、尿酸盐阴离子转运体1（

URAT1

）、

OAT1

和

GLUT9

mRNA表达。

结果

造模第14天，与空白组比较，化模高脂劳倦组、UOX

-/-

高脂劳倦组小鼠湿浊内蕴证候积分升高（

＜0.05）；第28天，两组湿浊内蕴证候积分明显增加且负重力竭游泳时间缩短（

＜0.01），提示湿浊内蕴证候模型制备成功。与空白组比较，其余各组小鼠肾脏指数及血清UA、XDH、XOD、BUN、TNF-α和IL-1β水平升高，肾脏组织

HIF

1α

、

URAT1

、

OAT1

和

GLUT9

mRNA表达升高，

ABCG2

mRNA表达降低（

＜0.01或

＜0.05）。与化模组和UOX

-/-

组比较，化模高脂劳倦组和UOX

-/-

高脂劳倦组可见更为明显的肾脏病理损伤，血清UA水平降低，BUN、TNF-α水平升

高（

＜0.05或

＜0.01），肾脏组织OAT1和GLUT9蛋白表达增加。

结论

化学诱导和基因敲除两种方法，叠加高脂饮食和负重力竭游泳，均可成功制备HUA湿浊内蕴证小鼠模型。其中，化学诱导法操作简单、成本低，适合短期药效筛选；UOX基因敲除使血尿酸水平自发升高，不依赖药物造模，可更好模拟人类代谢特征。

Abstract

Objective

To establish and evaluate a hyperuricemia （HUA） mouse model with the damp-turbidity internal accumulation syndrome.

Methods

Thirty-six C57BL/6J mice were randomly divided into control group， chemically induced model group （Model）， and model combined with high-fat and fatigue group （Model+HF）. Twenty-four uricase gene knockout （UOX

-/-

） mice were randomly divided into UOX

-/-

group and UOX

-/-

+HF group， with 12 mice in each group. The Model group and the Model+HF group established the HUA model by intragastric administration of potassium oxyazinate combined with adenine. The Model+HF group and the UOX

-/-

+HF group adopted a high-fat diet combined with weight-bearing exhaustive swimming to establish the HUA model with the damp-turbidity internal accumulation syndrome. On day 1， 7， 14， 21， and 28 after modeling， the damp-turbidity internal accumulation syndrome score of each group was evaluated. On day 1 and day 28， a weight-bearing swimming exhaustion test was performed， and the exhaustive swimming time was recorded. On day 28， liver and kidney indexes were calculated， and hematoxylin-eosin （HE） staining was used to observe histopathological changes in liver and kidney tissues. Serum levels of uric acid （UA）， xanthine dehydrogenase （XDH）， xanthine oxidase （XOD） and urea nitrogen （BUN） were detected through biochemical assays. ELISA was used to detect serum levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）. Immunohistochemistry was used to detect the protein expression of organic anion transporter 1 （OAT1） and glucose transporter 9 （GLUT9） in renal tissue

s. Quantitative real-time PCR （qRT-PCR） was used to detect the mRNA expressions of adenosine triphosphate binding transporter G2 （

ABCG2

）， hypoxia-inducible factor-1α （

HIF

1α

）， urate anion transporter 1 （

URAT1

）， and

GLUT9

in renal tissues.

Results

On day 14 of modeling， the damp-turbidity internal accumulation syndrome scores of mice in the Model+HF group and the UOX

-/-

+HF group were elevated compared with the control group（

＜0.05）； on day 28， the scores significantly increased， and the exhaustive swimming time was shortened （

＜0.01）， indicating successful establishment of the damp-turbidity internal accumulation syndrome model. Compared with the control group， all other groups exhibited increased kidney index， serum levels of UA， XDH， XOD， BUN， TNF-α， and IL-1β， elevated renal mRNA expression of

HIF

1α

，

URAT1

，

OAT1

， and

GLUT9

， and decreased renal

ABCG2

mRNA expression （

＜0.01 or

＜0.05）. Significant pathological damage in the kidney was observed in the Model+HF group and the UOX

-/-

+HF group compared to the Model group and the UOX

-/-

group， with decreased serum UA and increased BUN and TNF-α levels （

＜0.05 or

＜0.01）， as well as increased expression of OAT1 and GLUT9 in the renal tissue.

Conclusion

Both chemical induction and gene knockout， combined with a high-fat diet and weight-bearing exhaustive swimming， can successfully establish mouse models of HUA with damp-turbidity internal accumulation syndrome. Chemical induction is simple to operate and cost-effective， suitable for short-term drug screening， while UOX gene knockout induces spontaneous elevation of serum uric acid levels without drug administration， which may better mimick human metabolic characteristics.

关键词

Keywords

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