关键词: 高尿酸血症小鼠模型, 造模, 血尿酸检测, 微量采血

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