Tang Dong-Hong, Ye You-Song, Wang Chen-Yun, Li Zhe-Li, Zheng Hong, Ma Kai-Li
Medical Primate Research Center of China, Institute of Medical Biology, Chinese Academy of Medical Sciences/Peking Union Medical College, No. 935, Jiaoling Road, Kunming, Yunnan 650118, P.R. China.
Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, Yunnan 650504, P.R. China.
Exp Anim. 2017 Aug 5;66(3):209-216. doi: 10.1538/expanim.16-0096. Epub 2017 Mar 16.
Potassium oxonate, a selectively competitive uricase inhibitor, produced hyperuricemia (HUA) in rodents in a previous study. In this study, we employed the tree shrew as an animal model to study potassium oxonate-induced HUA. The effect of allopurinol (ALLO), a uric acid reducer, was also examined in this model. Potassium oxonate at doses of 5, 20, 40, 60, 80, 100, and 1,000 mg/kg was given intraperitoneally to tree shrews. The results showed that potassium oxonate can effectively increase the levels of uric acid in tree shrews at doses ranging from 40 to 100 mg/kg. Semiquantitative RT-PCR showed that the xanthine dehydrogenase/oxidase (XDH/XO) mRNA expression level was significantly higher in the liver tissue of tree shrews with high levels of uric acid. There were no changes in serum urea nitrogen, or serum creatinine values. ALLO can significantly decrease serum uric acid levels (P<0.01) and raise XDH/XO mRNA expression levels in the liver tissue of tree shrews with HUA. XDH/XO mRNA expression levels did not change in untreated tree shrews. Studies on acute toxicity in the tree shrew did not show any significantly abnormal signs. There were no adverse effects at the macroscopic level up to doses ≤100 mg/kg. Potassium oxonate induced acute HUA in tree shrews at lower doses compared with other animal models. Potassium oxonate-treated tree shrews may be a potential animal model for studying pathogenic mechanism and evaluating a new therapeutic agent for treatment of HUA in humans.
草酸钾是一种选择性竞争性尿酸酶抑制剂，在先前的一项研究中，它在啮齿动物中诱发了高尿酸血症（HUA）。在本研究中，我们采用树鼩作为动物模型来研究草酸钾诱导的高尿酸血症。还在此模型中检测了尿酸降低剂别嘌醇（ALLO）的作用。将剂量为5、20、40、60、80、100和1000mg/kg的草酸钾腹腔注射给树鼩。结果表明，草酸钾在40至100mg/kg的剂量范围内可有效提高树鼩的尿酸水平。半定量逆转录聚合酶链反应（RT-PCR）显示，尿酸水平高的树鼩肝脏组织中黄嘌呤脱氢酶/氧化酶（XDH/XO）mRNA表达水平显著更高。血清尿素氮或血清肌酐值没有变化。别嘌醇可显著降低高尿酸血症树鼩肝脏组织中的血清尿酸水平（P<0.01），并提高XDH/XO mRNA表达水平。未经治疗的树鼩中XDH/XO mRNA表达水平没有变化。对树鼩的急性毒性研究未显示任何明显异常体征。在剂量≤100mg/kg时，宏观水平上没有不良反应。与其他动物模型相比，草酸钾在较低剂量下即可诱导树鼩发生急性高尿酸血症。经草酸钾处理的树鼩可能是一种潜在的动物模型，用于研究人类高尿酸血症的发病机制和评估新的治疗药物。
