尿酸性肾病大鼠模型的建立

目的：考察4种不同的方法，建立稳定的尿酸性肾病（uAN）大鼠模型。方法：50只雄性SD大鼠随机分成5组，正常对照组实验过程中正常饲养；模型I、Ⅱ、Ⅲ组给予10％高酵母饲料喂养，同时分别给予腺嘌呤每日50mg／kg、100mg／kg、200mg／kg灌胃；模型Ⅳ组按腺嘌呤100mg／kg、乙胺丁醇250mg／kg的比例，配置成混悬液每日350mg／kg灌胃，连续给药2ld，制造UAN模型。实验前、实验第10天、第21天大鼠测定血清uA、BUN、CR水平；HE染色观察肾脏组织病理变化；免疫组化法观察。肾脏组织尿酸盐阴离子交换器1（uRAT1）、有机阴离子转运子1（OAT1）、有机阳离子转运体2（OCT2）的表达。结果：模型I组uA、BUN、CR水平较正常组轻微升高（P〉0．05）；模型Ⅱ组UA、BUN、CR水平在第10天、第21天较正常组升高（P〈0．05）；模型Ⅲ、Ⅳ组仅在第10天uA水平较正常组升高（P〈0．05）；BUN、CR水平在第10天、第21天，较正常组升高明显（P〈0．05）。HE染色病理切片结果提示：各模型组肾小管和间质均有不同程度的损伤，模型Ⅱ、Ⅲ、Ⅳ组肾组织内可见黄褐色结晶，其中模型Ⅲ、Ⅳ组肾组织存在广泛性损害。免疫组化法观察肾组织蛋白表达情况：模型Ⅱ、Ⅲ、Ⅳ组URAT1蛋白表达较正常组上调（P〈0．05，P〈0．01）；同时，OAT1、OCT2蛋白表达较正常组下调（P〈0．05，P〈0．01）。结论：采用酵母和腺嘌呤适合剂量联合用药，可建立稳定的UAN大鼠模型。

The Establishment of Rat Model with Uric Acid Nephropathy

Objective To establish the rat model of uric acid nephropalhy（UAN）. Methods Fifty SD rats were randomly divided into 5 groups： rats in control group were given normal diet; model group I , Ⅱ, Ⅲ were given 10% yeast and adenine at a dosage of 50rag- kg-1· d-1, 100mg·kg-1·d-1 and 200mg·kg-1·d-1 by gavage respectively. Then model IV was given adenine 100 mg. kg-1·d-1 and ethambutol 250 rag. kg-1·d-1 by gavage for 21 days. The levels of serum uric acid（UA）, blood urea nitrogen（BUN）, creatinine（CR） were respectively measured before the experiment, on the day of 10 th and 21 th. The pathological changes of renal tissue were observed by HE stainning and the expressions of Uratl, OAT 1 and OCT 2 were observed by immunohistodaemistl after their sacrifice. Results Compared with control group, the levels ofUA, BUN, CR of model group I were increased slightly （P ~ 0.05）, the levels of UA, BUN, CR of model group II were increased steady on the 10th and 21th day （P 〈 0.05）. The levels of UA of model group Ⅲ and model group Ⅳ were increased on 10th day （P 〈 0.05）, and the levels of BUN, CR of these two groups had a statistical significance on 10th and 21th day （P 〈0.01）. The results of pathological sections HE staining showed that the tubular and interstitial were injury in all 4 model groups, and there were various damgges of the renal tissue in model group Ⅲ and Ⅳ. Immunohisto- chemistry results showed that the expressions of URAT 1 in model Ⅱ, Ⅲand Ⅳ were increased （P 〈 0.05）, while expression of OAT 1 and OCT2 were decreased（P〈 0.05）, compared with the control group. Conclusion The rat model of uric acid nephropathy（UAN） has been successfully established with adenine and the diet of yeast.