目的 研究奥柳氮钠对氧嗪酸钾诱导的高尿酸血症小鼠嘌呤及尿酸代谢关键酶的影响。方法 昆明种小鼠60 只,随机分为6组,分别为正常组、模型组、奥柳氮钠组(3、6、12 mg·kg-1)及阳性药非布索坦组(1 mg·kg-1)。除非布索坦为灌胃给药外,其余各组分别腹腔给予相应剂量的药物或溶媒,每天2次,共5次。末次给药前1 h腹腔注射氧嗪酸钾(500 mg·kg-1)造模。末次给药1 h后取小鼠血液、肝脏及脑组织,检测小鼠血清尿酸、血清或组织中腺苷脱氨酶(ADA)、次黄嘌呤-鸟嘌呤磷酸核糖转移酶(HGPRT)、磷酸核糖焦磷酸合酶(PRPS)及磷酸核糖焦磷酸酰胺转移酶(PRPPAT)的蛋白或mRNA水平。同时检测奥柳氮钠体外对尿酸氧化酶的抑制作用。结果 奥柳氮钠可显著改善高尿酸血症小鼠的血尿酸水平,奥柳氮钠对高尿酸血症小鼠肝脏PRPPAT、PRPS及脑HGPRT的蛋白及mRNA水平无显著影响,奥柳氮钠可显著降低高尿酸血症小鼠的血清ADA水平,奥柳氮钠体外对尿酸氧化酶活性无显著影响。结论 奥柳氮钠对ADA的抑制作用可能是其治疗高尿酸血症的重要机理。
Abstract
OBJECTIVE To investigate the effects of olsalazine on the purine and uric acid metabolism key enzyme-ADA in potassium oxazine induced hyperuricemia mice. METHODS Sixty male Kunming mice were randomly divided into 6 groups,including normal, model, olsalazine sodium(3, 6, 12 mg·kg-1), and febuxostat (1 mg·kg-1) groups. Febuxostat group mice were administered with febuxostat twice a day for 2.5 days intragastrically and the others were intraperitoneally with vehicle or olsalazine sodium. Potassium oxazine were administered intraperitoneally 1 h before the last administration and the blood, liver and brain tissues were collected 1 h after the last administration to detect serum uric acid levels and protein or mRNA levels of ADA, HGPRT, PRPS and PRPPAT. At the same time, the in vitro inhibition effects of olsalazide on uricase were detected. RESULTS Olsalazide sodium treatment effectively improved the blood uric acid levels in hyperuricemia mice. Olsalazide sodium treatment has no effect on the protein and mRNA levels of liver PRPPAT, PRPS and brain HGPRT in hyperuricemia mice; Serum ADA levels were significantly decreased by olsalazide sodium treatment. Olsalazide sodium treatment didn't affect the uricase activity in vitro. CONCLUSION Serum ADA improving may be an important reason for the hyperuricemia treatment by olsalazine.
关键词
奥柳氮钠 /
高尿酸血症 /
嘌呤代谢 /
尿酸代谢
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Key words
olsalazine sodium /
hyperuricemia /
purine metabolism /
uric acid metabolism
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中图分类号：
R969.1
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参考文献
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脚注
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基金
云南省应用基础研究计划面上项目资助(2018FB149)
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