Establishment of uric acid associated nephropathy animal model and the underlying mechanisms

Abstract

Objective To establish an uric acid associated nephropathy (UAN) animal model and explore the mechanisms involved. Methods Eighteen (6-8 weeks old) male Sprague-Dawley rats weighed 200-220 g were randomly assigned into 2 groups: the control group (n=9), the uric acid associated nephropathy group (n=9). UAN rat model was established by oral administration of adenine (0.1g/kg) and potassium oxonate (1.5 g/kg) mixture daily for 3 weeks. After 3 weeks, the rats were sacrificed and blood and kidney samples were collected. Serum uric acid, creatinine and other biochemistry index were measured weekly. PAS and Masson staining were conducted to evaluate renal pathology and renal fibrosis. Serum activity of xanthine oxidase (XOD) was examined. Expression of p-EGFR and EGFR were detected by western blot and α-SMA expression was detected by immunohistochemical staining. Results After 3 weeks, the model group rats got 1.5 folds increased serum creatinine and significantly elevated serum uric acid. PAS and Masson staining showed that the UAN kidney developed glomerulosclerosis, tubulointerstitial damage and inflammatory cell infiltration. Serum activity of xanthine oxidase (XOD) was significantly upregulated in UAN group [(52.68±9.79) μmol/L vs (32.23±6.72) μmol/L, P<0.05]. Western blot showed that EGFR was activated and α-SMA expression increased remarkably in renal interstitial area of UAN rats. Conclusions The mixture of adenine and potassium oxonate can successfully establish UAN model. Phosphorylation of EGFR may mediate the activation of renal interstitial fibroblasts and accelerate the development and progression of UAN. Key words: Hyperuricemia; Receptor, epidermal growth factor; Actin