摘要
目的:用尿酸酶抑制剂氧嗪酸建立高尿酸血症大鼠模型,考察尿酸酶的体内降尿酸作用。方法:大鼠腹腔注射氧嗪酸钾建立高尿酸血症大鼠模型,尿酸酶滤菌后尾静脉注射给药;大鼠眼眶静脉采血,据对尿酸酶Vm/Km的改变测定血浆尿酸酶抑制剂含量,动力学尿酸酶法测定血浆尿酸水平。结果:每天腹腔注射氧嗪酸钾持续7 d后,大鼠血浆尿酸可维持在0.40 mmol/L以上,但大鼠体内尿酸酶抑制剂也维持在很高水平。持续给予氧嗪酸钾21 d,每只大鼠给予0.5 U聚乙二醇修饰尿酸酶,配对t检验发现血浆尿酸有统计显著性下降,但降幅小于12%;给予低剂量或未经修饰尿酸酶则血浆尿酸水平无显著变化。结论:用尿酸酶抑制剂建立的高尿酸血症动物模型评价尿酸酶的降尿酸作用可靠性有限。
Objective：To test the action of uricase to lower plasma urate in hyperuricemic rat model developed with oxonate. Methods： Potassium oxonate was given via intraperitoneal injection. Uricase after the filtration of bacteria was given via caudal vein injection. Blood samples were taken from orbital vein to determine equivalents of competitive inhibitors on uricase by their alteration on uricase Vm/Km and plasma uric acid levels by a direct kinetic uricase method. Results：After the continuous administration of potassium oxonate to rats once a day for one week ,plasma uric acid levels were kept over 0.40 mmol/L,meanwhile uricase-inhibiting substances were kept at steady high levels. To hyperuricemic rats after continued administration of potassium oxonate for 3 weeks,the injection of 0.5 U uricase modified with monoether poly （ethylene glycol）reduced plasma uric acid levels by paired t-test analysis with an average degree less than 12%. The injection of unmodified uricase or lower levels of modified uricase produced no expected action. Conclusion：Because of serious interference from the uricase inhibitor in rat in vivo,hyperuricemic rats developed with uricase inhibitors show limited reliability for evaluating the pharmacological actions of uricases.
出处
《重庆医科大学学报》
CAS
CSCD
北大核心
2010年第10期1454-1457,共4页
Journal of Chongqing Medical University
基金
国家自然科学基金(编号:30672009)
