尿酸排泄不良型高尿酸血症动物模型的建立

目的探讨构建尿酸排泄不良型高尿酸血症大鼠模型的可靠方法,为尿酸排泄不良型高尿酸血症发病机制的研究及治疗方案的优化奠定基础。方法采用氧嗪酸钾(300 mg/kg)分别与吡嗪酰胺(300 mg/kg)、乙胺丁醇(250 mg/kg)联合造模。连续给药1周、3周、5周,检测大鼠血、尿、便中尿酸水平,同时检测肝、肾功能,并进行组织学病理切片观察。结果氧嗪酸钾与乙胺丁醇联合造模组大鼠血尿酸出现先升高后降低的现象,而氧嗪酸钾与吡嗪酰胺联合造模组在连续给药期间血尿酸和尿液中尿酸升高平稳。两种方法对肝脏、肾脏均无明显损害。结论氧嗪酸钾与吡嗪酰胺联合能有效建立尿酸排泄不良型高尿酸血症大鼠模型,且模型稳定性好,其发病过程更符合临床尿酸排泄不良型高尿酸血症的病程。

Establishment of a rat model of hyperuricemia associated with uric acid excretion disorder

Objective To explore a reliable method to establish a rat model of hyperuricemia associated with abnormal uric acid excretion, and to lay the foundation for the study of pathogenesis of uric acid excretion disorder and the optimization of the treatment plan. Methods The models were established respectively by potasium oxonate(300 mg/kg) with pyrazinamide (300 mg/kg) or ethambutol(250 mg/kg). Continuous dosing for 1, 3 and 5 weeks, to determine the content of uric acid in rat blood, urine, and stool, the function of liver and kidney was detected and pathological examination was performed. Results The blood uric acid in the potasium oxonate and ethambutol group was increased first and then decreased, while in the potasium oxonate and pyrazinamide group were increased steadily and the excretion of uric acid in urine was stable during the continuous administration. The two methods showed no harmful effect on the liver and kidney function. Conclusions A stable rat model of hyperuricemia associated with uric acid excretion disorder can be effectively established by potassium oxonate and pyrazinamide, exhibiting similar manifestations of clinical hyperuricemia and uric acid excretion disorder.