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尿酸酶基因敲除小鼠中尿酸、尿囊素和8-羟基脱氧鸟苷的尿排泄情况。

Urinary excretion of uric acid, allantoin, and 8-OH-Deoxyguanosine in uricase-knockout mice.

作者信息

Inazawa K, Yamaguchi S, Hosoyamada M, Fukuuchi T, Tomioka N H, Yamaoka N, Kaneko K

机构信息

a Laboratory of Biomedical and Analytical Sciences, Faculty of Pharma-Science, Teikyo University , Tokyo , Japan.

b Laboratory of Human Physiology & Pathology, Faculty of Pharma-Science, Teikyo University , Tokyo , Japan.

出版信息

Nucleosides Nucleotides Nucleic Acids. 2016 Dec;35(10-12):559-565. doi: 10.1080/15257770.2016.1163376.

Abstract

Although uricase-knockout (Uox KO) mice are reported to develop uric acid (UA) nephropathy, those that mature without severe nephropathy could be useful for research into purine metabolism in humans. In this study, we measured the urinary excretion of creatinine, UA, allantoin, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) collected from Uox KO mice housed in metabolic cages. UA and allantoin were determined using liquid chromatography-mass spectrometry and creatinine and 8-OHdG were measured with a commercial kit. Uox KO mice excreted significantly higher levels of UA than wild-type mice (C57BL/6), while the excretion of allantoin was significantly lower. Urinary allantoin was detected in Uox KO mice despite a lack of uricase, which is the same as in humans. In contrast to the elevated levels of UA, the daily excretion of 8-OHdG, an oxidative stress marker, was lower in Uox KO mice. UA is thought to act as an anti-oxidizing agent in humans; thus, these results show that Uox KO mice are potential animal models for research into human purine metabolism.

摘要

尽管据报道尿酸酶基因敲除(Uox KO)小鼠会发展为尿酸(UA)肾病,但那些未出现严重肾病而成熟的小鼠可能对人类嘌呤代谢研究有用。在本研究中,我们测量了饲养在代谢笼中的Uox KO小鼠尿液中肌酐、UA、尿囊素和8-羟基-2'-脱氧鸟苷(8-OHdG)的排泄量。使用液相色谱-质谱法测定UA和尿囊素,用商业试剂盒测量肌酐和8-OHdG。Uox KO小鼠排泄的UA水平显著高于野生型小鼠(C57BL/6),而尿囊素的排泄量显著降低。尽管缺乏尿酸酶,但在Uox KO小鼠中仍检测到尿囊素,这与人类情况相同。与UA水平升高相反,氧化应激标志物8-OHdG的每日排泄量在Uox KO小鼠中较低。UA被认为在人类中起抗氧化剂的作用;因此,这些结果表明Uox KO小鼠是研究人类嘌呤代谢的潜在动物模型。

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