The Mechanism of False in Vitro Elevation of Uric Acid Level in Mouse Blood.
The Mechanism of False in Vitro Elevation of Uric Acid Level in Mouse Blood.
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DOI：
10.1248/bpb.b15-01046
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发表时间：
2016-07
影响因子：
2
通讯作者：
Tamaki Watanabe;N. H. Tomioka;Shigekazu Watanabe;Yoshihiko Suzuki;M. Tsuchiya;M. Hosoyamada
中科院分区：
文献类型：
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作者：
Tamaki Watanabe;N. H. Tomioka;Shigekazu Watanabe;Yoshihiko Suzuki;M. Tsuchiya;M. Hosoyamada
在室温下孵育30分钟可使试管中小鼠血液的尿酸（UA）水平升高，之前曾报道为“尿酸水平的假体外升高”。“然而，使用相同的孵育方法，人体血液的UA水平不会升高。我们使用具有B6-ChrXC（MSM）的高活性次黄嘌呤磷酸核糖转移酶（Hprt）的小鼠，Hprt基因位点中具有Mus musculus morocinus染色体部分的consomic小鼠品系，或具有尿酸氧化酶基因（Uox）靶向缺失（Uox敲除（KO））的小鼠，阐明了假体外UA升高的机制。用HPLC法测定血浆UA、次黄嘌呤和黄嘌呤的浓度，并与C57 BL/6 J实验室小鼠的血浆UA、次黄嘌呤和黄嘌呤浓度进行比较。Uox-KO小鼠的尿酸水平约为对照组的10倍，在试管中孵育后没有升高。与别嘌呤醇，次黄嘌呤水平的B6-ChrXC（MSM）和Uox-KO显着低于对照组。在不含别嘌呤醇的情况下，B6-ChrXC（MSM）的UA和黄嘌呤水平显著低于C57 BL/6 J对照组。即使使用别嘌呤醇，UA和黄嘌呤水平仍显著低于对照组。总之，“体外尿酸水平假性升高”似乎是由实验室小鼠红细胞HPRT活性水平低和血浆尿酸水平低引起的。
Thirty minutes incubation at room temperature elevates the uric acid (UA) level of mouse blood in a test tube, and has previously been reported as "false in vitro elevation of the uric acid level." However the UA level of human blood does not elevate using the same incubation. We clarified the mechanism of the false in vitro UA elevation using mice with highly active hypoxanthine phosphoribosyl transferase (Hprt) of B6-ChrXC(MSM), a consomic mouse strain with the chromosome portion of Mus musculus morocinus in the Hprt gene site, or mice with a targeted deletion of the urate oxidase gene (Uox) (Uox-knockout (KO)). The plasma levels of UA, hypoxanthine, and xanthine, determined by HPLC, were compared with those of C57BL/6J laboratory mice used as controls. The uric acid level of Uox-KO mice was approximately 10 times higher than that of control, did not elevated after incubation in the test tube. With allopurinol, the hypoxanthine levels of B6-ChrXC(MSM) and Uox-KO were significantly lower than that of controls. Without allopurinol, the UA and xanthine levels of B6-ChrXC(MSM) were significantly lower than those of C57BL/6J controls. Even with allopurinol, the UA and xanthine levels were still significantly lower than that of controls. In conclusion, "false in vitro elevation of uric acid level" seems to be caused by low levels of erythrocyte HPRT activity and the low plasma uric acid level of laboratory mice.