大鼠高尿酸血症模型的建立与研究

Establishment and study of a hyperuricemia rat model

目的建立一种大鼠高尿酸血症模型,并探讨高尿酸血症是否会产生继发性心血管疾病。方法将SPF级雄性SD大鼠32只随机分成正常对照组(Group C),氧嗪酸钾模型组(Group M1),氧嗪酸钾联合高糖高脂饲料模型组(Group M2),氧嗪酸钾联合酵母膏饲料模型组(Group M3),每组8只,连续造模3周。通过比较大鼠的血清尿酸(uric acid,UA),尿素氮(blood urea nitrogen,BUN),肌酐酸(creatinine,Cr),胰岛素(insulin,INS),血糖(blood glucose,GLU),甘油三酯(triglyceride,TG)等指标,并辅以病理学检查结果来对大鼠高尿酸血症模型进行研究。结果给予750 mg/kg体重氧嗪酸钾灌胃联合酵母膏饲料复制出的高尿酸血症模型大鼠,具有UA水平显著升高(P<0.01)、维持时间长、3/8大鼠的肾发生病变的特点,在产生高尿酸血症的同时还伴有GLU、INS和TG水平改变及3/8大鼠心脏的病变,提示继发性心血管病变的发生。结论氧嗪酸钾灌胃联合酵母膏饲料造模方法较单纯氧嗪酸钾造模更适用于大鼠长期高尿酸血症模型的建立,同时还伴随着继发性血糖紊乱的发生,因此该造模方案可用于高尿酸血症与心血管疾病的相互干预机制研究的动物模型,并进一步应用于高尿酸血症的治疗药物的临床前药效学综合评价。

Objective To establish a rat model of hyperuricemia, and explore the possible secondary cardiovascular disease that could be induced by hyperuricemia in the model rats. Methods 32 male SD rats were randomly divided into control group(Group C), potassium oxonate model group(Group M1), potassium oxonate combined with high-sugar model group(Group M2), potassium oxonate combined with yeast extract feed model group(Group M3), 8 rats were treated in each group for 3 weeks. At the end of the experiment, the serum levels of uric acid(UA), blood urea nitrogen, creatinine, insulin(INS), blood glucose(GLU) and triglyceride(TG) were measured, and histopathological examination of liver, renal, and heart tissue was performed. Results Compared with the control group, a significant increase in serum levels of UA(P<0.01) and the number of rats showing renal lesions was found in the experimental group(3/8, 37.5%) after oral administration of potassium oxonate at a dose of 750 mg/kg, combined with yeast extract feed(Group M3). Also, the changes in GLU, INS, TG and the histopathology of heart tissue(3/8, 37.5%) suggesting that rats in this group had secondary cardiovascular alterations. Conclusions Compared with the basic potassium oxonate model, the model of potassium oxonate combined with yeast extract feed is more suitable for the study of rat chronic hyperuricemia, accompanied by glucose metabolic impairment. It can also be used in rat models to establish mutual intervention mechanisms between hyperuricemia and cardiovascular disorders, and be applied in comprehensive preclinical pharmacodynamic evaluation of therapeutic drugs for hyperuricemia.