氧嗪酸钾致小鼠急性高尿酸血症动物模型的研究及评价  

Study and evaluation of potassium oxonate-induced acute hyperuricemia animal model

作　　者：王陈芸 李哲丽[1] 叶尤松[1] 易红昆[1] 蔡发晶 肖涵 唐东红[1] Wang Chenyun;Li Zheli;Ye Yousong;Yi Hongkun;Cai Fajing;Xiao Han;Tang Donghong(Institute of Medical Biology , Chinese Academy of Medical Science /Peking Union Medical College, Kunming 650118;Yunnan University of Traditional Chinese Medicine, Kunming 650118)

机构地区：[1]中国医学科学院/北京协和医学院医学生物学研究所小动物实验部,昆明650118 [2]云南省中医学院中药学院,昆明650200

出　　处：《中药药理与临床》2019年第1期176-180,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：中国医学科学院医学与健康科技创新工程重大协同创新项目(编号:2016-I2M-2-006)

摘　　要：目的:通过对小鼠梯度给药,探讨氧嗪酸钾致小鼠高尿酸血症急性模型的用药剂量,并对不同的高尿酸血症动物模型进行比较,为高尿酸血症研究中动物模型的选择提供参考。方法:小鼠腹腔注射不同剂量氧嗪酸钾,诱导体内尿酸蓄积,在一定时间段内对小鼠进行尾静脉采血,测定血清尿酸值,得到小鼠急性高尿酸血症模型氧嗪酸钾合适剂量;再利用实时荧光定量技术检测小鼠给药后肝脏黄嘌呤氧化/脱氢酶基因表达水平的变化。依据文献显示的大鼠和树鼩高尿酸血症动物模型氧嗪酸钾用量和肝脏黄嘌呤氧化/脱氢酶mRNA表达水平的变化对三种动物模型进行分析比较。结果:小鼠腹腔注射600 mg/kg的氧嗪酸钾在给药后1～2 h时能形成较为稳定的急性高尿酸血症;腹腔注射氧嗪酸钾1.5h后,小鼠黄嘌呤氧化酶/脱氢酶mRNA的表达水平较对照组上升2.14倍。综合本实验结果和文献分析显示氧嗪酸钾致三种动物高尿酸血症的用药剂量不同,其中树鼩所需最小。结论:尿酸酶抑制剂氧嗪酸钾均能诱导出大鼠、小鼠和树鼩急性高尿酸模型,但药物的敏感性差异较大,提示树鼩可作为一种潜在的高尿酸动物模型。objective: To study the differences of potassium oxonate-induced acute hyperuricemia models in the rat,the mouse and the tree shrew,and to explore its appropriate dosage. Methods: Different doses of potassium oxonate were intraperitoneally administered to mice to induce uric acid accumulation. Tail vein blood was collected at specific time points to measure serum uric acid values,in order to determine a suitable potassium oxonate dose for mouse acute hyperuricemia model. Real-time fluorescence quantitative polymerase chain reaction was used to measure changes in gene expression levels of liver xanthine oxidase/dehydrogenase in mice after the administration of potassium oxonate. The three animal models were then compared according to the potassium oxonate doses and liver xanthine oxidase/dehydrogenase mRNA expression levels. Results: Acute hyperuricemia were established 1 ~ 2 h after intraperitoneal injection of 600 mg/kg potassium oxonate to mice.Compared to the control group,the mRNA expression levels of xanthine oxidase/dehydrogenase increased 2. 14 times after 1. 5 h of potassium oxonate injection. Acute hyperuricemia models were established in three animals under different dosages,while the minimum dose was observed in the tree shrew.Conclusion: The results of experiments suggests that tree shrews may be a potential hyperuricemia animal model.

关 键 词：小鼠 大鼠 树鼩 氧嗪酸钾 高尿酸血症 黄嘌呤氧化酶/脱氢酶 

分 类 号：R589.7[医药卫生—内分泌] R-332[医药卫生—内科学]