Abstract: Objective　In order to explore the dynamic changing regularity of each physiological index on acute hyperuricemia model in rats.Methods　The acute hyperuricemia rat model was established by the intraperitoneal injection of hypoxanthine and subcutaneous injection of oteracil potassium in different doses. At 2, 4, 8 and 12 hours after modeling, 6 animals were taken respectively to determine blood uric acid, blood creatinine, serum urea nitrogen and serum. The activity of xanthine oxidase (XOD) in the liver was examined and the renal histopathological test was conducted.Results　Hypoxanthine combined with oteracil potassium can successfully establish hyperuricemia model in rats. Two hours after administration of 100 mg/(kg·bw) hypoxanthine and oteracil potassium, the level of serum uric acid was significantly increased (P<0.05), but the level of serum creatinine and serum urea nitrogen did not increase significantly. However, when the dose of oteracil potassium was increased to 200 mg/(kg·bw), 4 h after modeling, the level of serum creatinine and serum urea nitrogen was increased significantly (P< 0.05). We also found that the degree and duration of the model were direct proportionality to the dose of  hypoxanthine and oteracil potassium, and the levels of serum uric acid, serum creatinine and serum urea nitrogen showed certain dynamic changing regularity. In addition, the pathological damages of kidney were found in each dose group, and the damage scope expanded with time. Finally, in the situation of acute attacks of hyperuricemia, no significant changes of xanthine oxidase (XOD) activity in serum and liver were observed.Conclusion　When establishing acute hyperuricemia model in rats, it may be suitable that the dosage range of hypoxanthine is between 100-300 mg/(kg·bw), and the dosage range of potassium oxazinate dose is between 100-200 mg/(kg·bw).

Key words: hyperuricemia, disease model, uric acid, time factors

摘要： 目的　通过对急性高尿酸血症大鼠模型不同造模条件的摸索,探讨各生理指标的动态变化规律,并获取模型 随时间变化特点,确立较优造模条件。方法　本急性高尿酸血症大鼠模型采用腹腔注射不同剂量次黄嘌呤联合皮 下注射不同剂量氧嗪酸钾的方法造模,造模后2、4、8和12 h分别取6只动物,测定血尿酸、血肌酐、血清尿素氮、血 清和肝黄嘌呤氧化酶(XOD)活性并进行肾组织病理学检测。结果　次黄嘌呤和氧嗪酸钾联合给药造模,建立大鼠 高尿酸血症模型,给予100 mg/(kg·bw)剂量的次黄嘌呤及氧嗪酸钾2 h后,即可引起大鼠血尿酸水平的显著升高 (P<0.05),但血肌酐及血清尿素氮水平未见显著升高。当氧嗪酸钾剂量提高至200 mg/(kg·bw)时,建模后4 h 可见血肌酐及血清尿素氮的显著升高(P<0.05)。模型程度及持续时间与次黄嘌呤、氧嗪酸钾的剂量成正比关 系。血尿酸、血肌酐、血清尿素氮水平各自呈现出一定的动态变化规律。各剂量组动物均发现肾的病理损伤,损 伤范围随时间的推移而扩大。高尿酸血症的急性发作未见血清及肝黄嘌呤氧化酶(XOD)活性的明显变化。 结论　成功建立大鼠急性高尿酸血症模型,次黄嘌呤剂量在100~300 mg/(kg·bw),氧嗪酸钾剂量在100~200 mg/(kg·bw)是较为合适的造模条件。

关键词: 高尿酸血症, 疾病模型, 尿酸, 时间因素