氧嗪酸钾致小鼠急性高尿酸血症动物模型的研究及评价

详细信息    查看全文 | 推荐本文 |

英文篇名：Study and evaluation of potassium oxonate-induced acute hyperuricemia animal model 作者：王陈芸 ; 李哲丽 ; 叶尤松 ; 易红昆 ; 蔡发晶 ; 肖涵 ; 唐东红 英文作者：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;Yunnan University of Traditional Chinese Medicine; 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 英文关键词：rat;;mouse;;tree shrew;;potassium oxonate;;hyperuricemia;;xanthine oxidase/dehydrogenase 中文刊名：ZYYL 英文刊名：Pharmacology and Clinics of Chinese Materia Medica 机构：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;云南省中医学院中药学院; 出版日期：2019-02-15 出版单位：中药药理与临床 年：2019 期：v.35;No.199 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) 语种：中文; 页：ZYYL201901039 页数：5 CN：01 ISSN：51-1188/R 分类号：178-182

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.

引文

[1]Zhu Y, Pandya B J, Choi H K. Prevalence of gout and hyperuricemia in the US general popμLation: the National Health and Nutrition Examination Survey 2007-2008.Arthritis Rheum,2011,(63)∶3136～3141.
    [2]Alexander G, Vandell, Caitrin W, et al. J Intern Med. Hydrochlorothiazide-induced hyperuricaemia in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study,2014,276(5)∶486～497.
    [3]杨旭娟,黄茜,田周,等.以PNP酶为靶点的急性高尿酸血症小鼠模型组建.中国药理学通报,2017,33(6)∶882～885.
    [4]Kimiyoshi I, Hirotaka M S, Tappei T, et al. Decreased extra-renal urate excretion is a common cause of hyperuricemia.Nat Commun,2012,(3)∶ 764.
    [5]陈刚,谭明亮.茶多酚对高尿酸血症小鼠尿酸产生与排泄的影响及机制研究.中国药理学通报,2017,33(2)∶218～222.
    [6]陈刚,贾萍.别嘌醇改善果糖诱导的大鼠高尿酸血症与调节肠道葡萄糖转运子表达的关系研究.中国药理学通报,2017,33(4)∶469～474.
    [7]刘李玟韬,杨洁,陈秉朴.高尿酸血症动物模型研究述评.湖南中医药大学学报,2017,(12)∶1431～1436.
    [8]安海文,李燕林,刘琳娜,等.祛湿泄浊合剂对高尿酸血症模型小鼠血清尿酸以及肾脏XOD、ADA的影响.河南中医,2016,(3604)∶600～602.
    [9]陈露滢,杨继国,邱晓斌,等.土茯苓复方制剂对氧嗪酸钾致高尿酸血症改善作用的研究.现代食品科技,2013,(2911)∶2649～2652.
    [10]王陈芸,李哲丽,叶尤松,等.氧嗪酸钾致Wistar大鼠高尿酸血症急性模型的剂量探讨.中药药理与临床,2018,34(5)∶141～143.
    [11]Tang D H,Ye Y S,Wang C Y,et al. Potassium oxonate induces acute hyperuricemia in the tree shrew (tupaia belangeri chinensis).Exp Anim, 2017,(663)∶ 209～216.
    [12]Park J E, Yeom Z, Park K T,et al. Hypouricemic Effect of Ethanol Extract of Aster glehni Leaves in Potassium Oxonate-Induced Hyperuricemic Rats. Clin Nutr Res.,2018,(7)∶126～135.
    [13]He H M, Feng Y L, ZHang W G,et al.Research progress on the establishment of hyperuricemia animal models by different methods. Jiangxi Journal of Traditional Chinese Medicine, 2015,(4612)∶ 72～75.