LI Qin,LIU Jie,LIU Xianjun,et al.Establishment of rat model of hyperuricemia by feeding potassium oxonate combined with fructose[J].J Third Mil Med Univ,2018,40(07):569-576.

果糖联合氧嗪酸钾建立高尿酸血症大鼠模型(/HTML )




Establishment of rat model of hyperuricemia by feeding potassium oxonate combined with fructose
LI Qin LIU Jie LIU Xianjun JIANG Xue

Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China

hyperuricemia animal model fructose potassium oxonate rats
R-332; R589.7; R977.6

目的    采用单纯果糖及联合氧嗪酸钾喂养的方法诱导高尿酸血症(hyperuricemia,HUA)大鼠模型,比较不同模型的稳定性和适用性。方法     雄性SD大鼠60只,应用随机数字表法分为6组,每组10只,分别予以5%果糖水喂养(5%Fru组)、5%果糖水+氧嗪酸钾处理(5%FO组)、10%果糖水喂养(10%Fru组)、10%果糖水+氧嗪酸钾处理(10%FO组)、氧嗪酸钾处理(Oaps组)、清水喂养对照组(Con组)。实验造模14周,每周末检测大鼠血清尿酸(serum uric acid,SUA)、血清尿素氮(serum urea nitrogen,BUN)、血清肌酐(serum creatinine,SCr)水平,实验结束后观察大鼠肝、肾组织学变化。结果     5%FO组、10%Fru组、10%FO组均能快速升高SUA(P<0.01);在第10、11周10%Fru组SUA水平显著低于5%FO组、10%FO组(P<0.01)。10%Fru组、10%FO组BUN和SCr水平分别在第6、7周开始升高(P<0.01)。10%Fru组、10%FO组肾脏组织学改变明显;5%FO组偶见轻微组织学改变;各组均未发现肝脏有明显组织学变化。结论     果糖联合氧嗪酸钾能够成功建立稳定、高效的高尿酸血症大鼠模型,不同果糖浓度对肾脏损伤程度不同,可根据后续研究选择合适的动物模型。


Objective     To compare the stability and applicability of rat models of hyperuricemia induced by simple fructose feeding or feeding with potassium oxonate and fructose. Methods     A total of 60 male SD rats were randomly divided into 6 groups (10 animals in each group), that is, 5% Fru group (fed with normal chow diet and water containing 5% fructose), 5% FO group (water containing 5% fructose and potassium oxonate), 10%Fru group (water containing 10%), 10%FO group (water containing 10% fructose and potassium oxonate), Oaps group (water containing potassium oxonate), and control group (normal water). The experiment lasted for 14 weeks, and the levels of serum uric acid (SUA), urea nitrogen (BUN) and serum creatinine (SCr) were measured at every weekend. The pathological changes of the liver and kidneys were observed at the end of experiment. Results     5%FO group, 10%Fru group and 10%FO group rapidly increased the SUA level (P<0.01). At weeks 10 and 11, the level of SUA was significantly lower in the 10% Fru group than the 5%FO group and 10% FO group (P<0.01). The levels of BUN and SCr were gradually increased since weeks 6 and 7 in the 10%Fru group and 10%FO group (P<0.01). Obviously histological features were observed in the kidneys of the rats from the 10%Fru group and 10%FO group, but the changes were mildly in the kidney of the 5%FO group. There were no significant morphological changes in the liver of the rats from all the groups. Conclusion     Fructose combined with potassium oxonate can successfully establish a stable and highly effective rat model of hyperuricemia. Different doses of fructose show different effects on renal damage, and can be used for the animal models for different studies.


[1]RYU S, CHANG Y, ZHANG Y, et al. A cohort study of hyperuricemia in middleaged South Korean men[J]. Am J Epidemiol, 2012, 175(2): 133-143. DOI: 10.1093/aje/kwr291.
[2]KARIS E, CRITTENDEN D B, PILLINGER M H. Hyperuricemia, gout, and related comorbidities: cause and effect on a twoway street[J]. South Med J, 2014, 107(4): 235-241. DOI: 10.1097/SMJ.0000000000000082.
[3]GORAN M I, ULIJASZEK S J, VENTURA E E. High fructose corn syrup and diabetes prevalence: A global perspective[J]. Glob Public Health, 2013, 8(1): 55-64. DOI: 10.1080/17441692.2012.736257.
[4]SCHWARZ J M, NOWOROLSKI S M, WEN M J, et al. Effect of a highfructose weight-maintaining diet on lipogenesis and liver fat[J]. J Clin Endocrinol Metab, 2015, 100(6): 2434-2442. DOI: 10.1210/jc. 20143678.
[5]MALIK A H, AKRAM Y, SHETTY S, et al. Impact of sugar-sweetened beverages on blood pressure[J]. Am J Cardiol, 2014, 113(9): 1574-1580. DOI: 10.1016/j.amjcard.2014.01.437.
[6]李丽玉, 林志健, 张冰, 等. 连续高果糖饮水对大鼠尿酸水平的影响及其病理机制[J]. 中华临床营养杂志, 2014, 22(6): 368-374.DOI:3760/cma.j.issn.1674-635X. 2014. 06. 009.
LI L Y, LIN Z J, ZHANG B, et al. Effect of high fructose drinking water on uric acid level in rats and the underlying pathological mechanism[J]. Chin J Clin Nutr, 2014, 22(6): 368-374.DOI:3760/cma.j.issn. 1674-635X. 2014. 06. 009.
[7]CHEN G, JIA P. Allopurinol decreases serum uric acid level and intestinal glucose transporter5 expression in rats with fructose-induced hyperuricemia[J]. Pharmacological Rep, 2016, 68(4): 782-786. DOI: 10.1016/j.pharep.2016.04.014.
[8]ZHU C, TAI L L, WAN X C, et al. Comparative effects of green and black tea extracts on lowering serum uric acid in hyperuricemic mice[J]. Pharm Biol, 2017, 55(1): 2123-2128. DOI: 10.1080/13880209.2017. 1377736.
[9]ZHU L, DONG Y, NA S, et al. Saponins extracted from Dioscorea collettii rhizomes regulate the expression of urate transporters in chronic hyperuricemia rats[J]. Biomed Pharmacother, 2017, 93: 88-94. DOI: 10.1016/j.biopha.2017.06.022.
[10]CHEN Y, CHEN X L, XIANG T, et al. Total saponins from dioscorea septemloba thunb reduce serum uric acid levels in rats with hyperuricemia through OATP1A1 up-regulation[J]. J Huazhong Univ Sci Technolog Med Sci, 2016, 36(2): 237-242. DOI:  10.1007/s11596-016-1573-z.
[11]LIU Z, CHEN T, NIU H, et al. The establishment and characteristics of rat model of atherosclerosis induced by hyperuricemia[J]. Stem Cells Inter, 2016, 2016: 1-7. DOI: 10.1155/2016/1365257.
[12]别凤仪, 姜懿宸, 葛冰, 等. 酵母联合高果糖饲料对大鼠嘌呤代谢影响[J].营养学报, 2017, 39(2): 144-150. DOI: 10.13325/j.cnki.acta.nutr.sin.2017.02.010.
BIE F Y, JIANG Y C, GE B, et al. Effect of diet supplemented with yeast and high fructose on purine metabolism in rats[J]. Acta Nutrimenta Sin, 2017, 39(2): 144-150. DOI: 10.13325/j.cnki.acta.nutr.sin.2017.02.010.
[13]DALBETH N, PHIPPSGREEN A, HOUSE M E, et al. Body mass index modulates the relationship of sugar-sweetened beverage intake with serum urate concentrations and gout[J]. Arthr Res Ther, 2015, 17(1): 1-7. DOI: 10.1186/s13075-015-0781-4.
[14]CALICETI C, CALABRIA D, RODA A, et al. Fructose intake, serum uric acid, and cardiometabolic disorders: a critical review[J]. Nutrients, 2017, 9(4): 395. DOI: 10.3390/nu9040395.
[15]ABDULLA M H, SATTAR M A, ABDULLAH N A, et al. The effect of high-fructose intake on the vasopressor response to angiotensin Ⅱ and adrenergic agonists in Sprague-Dawley rats[J]. Pak J Pharm Sci, 2013, 26(4):727-732.
[16]LECOULTRE V, EGLI L, THEYTAZ F, et al. Fructoseinduced hyperuricemia is associated with a decreased renal uric acid excretion in humans[J]. Diabetes Care, 2013. 36(9): e149-e150. DOI: 10.2337/dc130866.
[17]XILIFU D, ABUDULA A, REHEMU N, et al. Effect of rosuvastatin on hyperuricemic rats and the protective effect on endothelial dysfunction[J]. Exp Ther Med, 2014, 8(6): 1683-1688. DOI: 10.3892/etm.2014.2027.
[18]CHEN H L, TSAI T C, TSAI Y C, et al. Kefir peptides prevent highfructose corn syrupinduced nonalcoholic fatty liver disease in a murine model by modulation of inflammation and the JAK2 signaling pathway[J]. Nutr Diabetes, 2016, 6(12): e237. DOI: 10.1038/nutd.2016.49.
[19]CHRISTOPHER, LEUNG, CHANDANA, et al. Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease[J]. World J Gastroenterol, 2016, 22(35): 8026-8040. DOI: 10.3748/wjg.v22.i35.8026.


 WANG Yu-qi,ZHENG Xin,ZHOU Nai-kang,et al.Biodistribution and PET imaging of 18F-fluoromisonidazole in murine model of lung carcinoma[J].J Third Mil Med Univ,2007,29(07):1794.
 LI Zhong,YANG Liu,DAI Gang,et al.Establishment of animal models of bilateral knee joint osteoarthritis by arthroscopy[J].J Third Mil Med Univ,2007,29(07):919.
 LI Cai-xia,WANG Feng-ying,LI Yu-yan,et al.Establishment of mouse model of premature ovarian failure[J].J Third Mil Med Univ,2008,30(07):506.
 MA Yu-xia,WANG Lin,KONG Yan,et al.Establishment of animal model of endometriosis in Bama miniature pigs[J].J Third Mil Med Univ,2008,30(07):530.
 GONG Guo-qi,MENG Hui,XIA Yong-zhi,et al.Experimental chronic hydrocephalus after intraventricular hemorrhage in rats: establishment of animal model and pathological observation[J].J Third Mil Med Univ,2008,30(07):969.
 CHEN Xiu-ming,AI Guo-ping,SU Yong-ping,et al.Effect of a novel isoflavone compound on plasma lipid and cholesterol of ovarectomied rats[J].J Third Mil Med Univ,2007,29(07):1559.

更新日期/Last Update: 2018-04-09