以PNP酶为靶点的急性高尿酸血症小鼠模型组建
发布时间：2018-10-21 14:46
【摘要】：目的建立一种新的急性高尿酸血症小鼠模型并利用该模型对PNP酶抑制剂Ulodesine进行体内药效作用评价。方法小鼠腹腔注射肌苷(inosine)和皮下注射氧嗪酸钾(oteracil potassium)诱导体内尿酸蓄积,在一定时间段内对小鼠进行内眦静脉或摘眼球采血,测定血清尿酸值,判断小鼠急性高尿酸血症模型成功与否;再利用酶动力学分析Ulodesine对PNP酶的体外抑制作用,并于造模前给予小鼠灌胃Ulodesine,造模后测定血清尿酸值,评价Ulodesine的降血尿酸作用。结果小鼠腹腔注射200 mg·kg~(-1)肌苷联合皮下注射200 mg·kg~(-1)氧嗪酸钾在1.5 h时能形成较为稳定的急性高尿酸血症;酶动力学测定结果显示Ulodesine对PNP酶有极强的抑制作用,其IC_(50)值为2.293 nmol·L~(-1);另外,Ulodesine的体内药效表明,Ulodesine能够明显减低急性高尿酸血症小鼠体内尿酸水平。结论我们已经成功地建立了一种新的急性高尿酸血症小鼠模型,该造模制作方法更简单有效,且该模型可以应用于验证PNP酶抑制剂。
[Abstract]:Objective to establish a new mouse model of acute hyperuricemia and evaluate the in vivo pharmacodynamics of PNP enzyme inhibitor Ulodesine. Methods the accumulation of uric acid in mice was induced by intraperitoneal injection of inosine (inosine) and subcutaneous injection of potassium oxazinate (oteracil potassium). The blood samples were collected from the inner canthus vein or eyeball of the mice in a certain period of time, and the serum uric acid levels were measured. To judge the success of acute hyperuricemia model in mice, to analyze the inhibitory effect of Ulodesine on PNP enzyme in vitro by enzyme kinetics, and to determine the serum uric acid value after mice were given Ulodesine, before making model, and to evaluate the effect of Ulodesine on reducing uric acid. Results after intraperitoneal injection of 200 mg kg~ (-1) inosine and subcutaneous injection of 200 mg kg~ (-1) potassium oxazinate, stable acute hyperuricemia was formed in mice, and the results of enzyme kinetics test showed that Ulodesine had a strong inhibitory effect on PNP enzyme. Its IC_ _ (50) value was 2.293 nmol L ~ (-1). In addition, the in vivo pharmacodynamics of Ulodesine showed that Ulodesine could significantly reduce the level of uric acid in mice with acute hyperuricemia. Conclusion We have successfully established a new acute hyperuricemia mouse model. The method is simpler and more effective, and the model can be used to verify the PNP enzyme inhibitor.
【作者单位】： 昆药集团股份有限公司药物研究院生物学部;
【基金】：云南省科技厅高层次科技创新人才计划(No 2013HA018)
【分类号】：R-332;R965
本文编号：2285422
[Abstract]:Objective to establish a new mouse model of acute hyperuricemia and evaluate the in vivo pharmacodynamics of PNP enzyme inhibitor Ulodesine. Methods the accumulation of uric acid in mice was induced by intraperitoneal injection of inosine (inosine) and subcutaneous injection of potassium oxazinate (oteracil potassium). The blood samples were collected from the inner canthus vein or eyeball of the mice in a certain period of time, and the serum uric acid levels were measured. To judge the success of acute hyperuricemia model in mice, to analyze the inhibitory effect of Ulodesine on PNP enzyme in vitro by enzyme kinetics, and to determine the serum uric acid value after mice were given Ulodesine, before making model, and to evaluate the effect of Ulodesine on reducing uric acid. Results after intraperitoneal injection of 200 mg kg~ (-1) inosine and subcutaneous injection of 200 mg kg~ (-1) potassium oxazinate, stable acute hyperuricemia was formed in mice, and the results of enzyme kinetics test showed that Ulodesine had a strong inhibitory effect on PNP enzyme. Its IC_ _ (50) value was 2.293 nmol L ~ (-1). In addition, the in vivo pharmacodynamics of Ulodesine showed that Ulodesine could significantly reduce the level of uric acid in mice with acute hyperuricemia. Conclusion We have successfully established a new acute hyperuricemia mouse model. The method is simpler and more effective, and the model can be used to verify the PNP enzyme inhibitor.
【作者单位】： 昆药集团股份有限公司药物研究院生物学部;
【基金】：云南省科技厅高层次科技创新人才计划(No 2013HA018)
【分类号】：R-332;R965
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1 徐立;时乐;赵芳;谭秋薇;姚金梁;;大鼠急性高尿酸血症模型的复制方法初探[J];中国药理学通报;2007年07期
，本文编号：2285422
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