Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China.
Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae (Tianjin University of Traditional Chinese Medicine), Ministry of Education, 312 Anshanxi Road, Nankai District, Tianjin 300193, China.
Int J Mol Sci. 2020 Jul 22;21(15):5178. doi: 10.3390/ijms21155178.
Hyperuricemia is an important risk factor of chronic kidney disease, metabolic syndrome and cardiovascular disease. We aimed to assess the time-feature relationship of hyperuricemia mouse model on uric acid excretion and renal function. A hyperuricemia mouse model was established by potassium oxonate (PO) and adenine for 21 days. Ultra Performance Liquid Chromatography was used to determine plasma uric acid level. Hematoxylin-eosin staining was applied to observe kidney pathological changes, and Western blot was used to detect renal urate transporters' expression. In hyperuricemia mice, plasma uric acid level increased significantly from the 3rd day, and tended to be stable from the 7th day, and the clearance rate of uric acid decreased greatly from the 3rd day. Further study found that the renal organ of hyperuricemia mice showed slight damage from the 3rd day, and significantly deteriorated renal function from the 10th day. In addition, the expression levels of GLUT9 and URAT1 were upregulated from the 3rd day, while ABCG2 and OAT1 were downregulated from the 3rd day, and NPT1 were downregulated from the 7th day in hyperuricemia mice kidney. This paper presents a method suitable for experimental hyperuricemia mouse model, and shows the time-feature of each index in a hyperuricemia mice model.
高尿酸血症是慢性肾脏病、代谢综合征和心血管疾病的重要危险因素。本研究旨在评估高尿酸血症小鼠模型尿酸排泄和肾功能的时间特征关系。通过氧嗪酸钾（PO）和腺嘌呤建立高尿酸血症小鼠模型 21 天。采用超高效液相色谱法测定血浆尿酸水平。苏木精-伊红染色观察肾脏病理变化，Western blot 检测肾脏尿酸转运体的表达。在高尿酸血症小鼠中，第 3 天血浆尿酸水平显著升高，第 7 天趋于稳定，尿酸清除率从第 3 天开始显著下降。进一步研究发现，高尿酸血症小鼠肾脏从第 3 天开始出现轻微损伤，第 10 天肾功能明显恶化。此外，高尿酸血症小鼠肾脏中 GLUT9 和 URAT1 的表达水平从第 3 天开始上调，而 ABCG2 和 OAT1 从第 3 天开始下调，NPT1 从第 7 天开始下调。本研究提出了一种适合实验性高尿酸血症小鼠模型的方法，显示了高尿酸血症小鼠模型中各指标的时间特征。
