Fructose Combined Yeast Induced Hyperuricemia Model And Mechanism Of Metabolism Of Uric Acid In Rats

Objective: Along with continuous elevation of the prevalence of hyperuricemia,more and more attention was attracted on how to establish a stable animal hyperuricemia model.At present,the modelling method was still controversial,and there still were some problems in the existing animal models.Therefore,we establish the rat model of hyperuricemia by a diet of combined fructose and yeast,in order to explore its effect and mechanism on purine metabolism by uric acid production and excretion pathway.Methods: A total of 50 rats were randomly divided into 5 groups: the control group were fed with a standard diet,the yeast group with yeast extract,the fructose group with 10%D-fructose,the yeast-oteracil potassium group(traditional model of hyperuricemia)with yeast extract and potassium oxonate [500mg/(kg · d),i.g]as a positive model,the yeast-fructose group with yeast extract and 10% D-fructose.At week 2,4,6 and 8,blood samples(1.5ml)were collected by cutting the tails of the rats,and serum uric acid(SUA),serum urea nitrogen(BUN),serum creatinine(SCr)concentrations were determined.After week 8,the urine was collected for 24 hours,and the urinary uric acid(UUA)and urinary creatine(UCr)levels were monitored to calculate clearance of uric acid(CUA)and endogenous creatinine clearance rate(CCR);serum xanthine oxidase(XOD)and serum adenosine deaminase(ADA)activity were determined and the sections of renal histopathology were observed.The protein levels of organic anion transporters 1(OAT1),renal-specific transporter(RST),glucose transporter 9(GLUT9)in kidney were detected by western blotting.Results: At week 2,4,6 and 8,SUA levels in the yeast-fructose group(345.9,403.7,447.2 and 451.4 ?mol/L)were respectively increased by 66.5%,33.8%,37.5% and 69.8%compared with the control group(all P<0.05).It was showed a significant increase of SUA concentration in the yeast-oteracil potassium group compared with the control groups(all P<0.05),which were increased by 28.79%?54.4%?39.4% and 75.1%.At the end of week 2,the SUA level of the yeast-fructose group was significantly higher than those of the yeast group,the fructose group and the yeast-oteracil potassium group(increased by 31.7%,52.9%,29.3%,respectively),which indicated that the SUA was increased fastest in yeast-fructose group.At week 8,the SUA levels of the yeast-fructose group and the yeast-oteracil potassium group were 2.24 and 2.17 times higher than the control group.In the yeast-fructose group,XOD and ADA activities in serum and 10%liver homogenate(46.3U/L and 10.4U/L,26.8U/L and 15.3U/L)were significant higher than the control group(38.2U/L and 7.7U/L,19.5U/L and 11.1U/L,all P<0.05).Compared with the control group,the 24 h urine volume increased significantly and CUA decreased significantly(all P<0.05).In the yeast-fructose group,occasional crystalline substance deposition and no obvious fibrosis were found in renal tubule lumen,and renal tubular and glomerular structures were normal by the histological features.Also in the yeast-fructose group,OAT1 levels were lower and RST levels were higher than the control group(all P<0.05).Conclusions: Fructose could enhance the role of yeast induced hyperuricemia.It could be used as a good model for the study of purine metabolism,which had less adverse effect on kidney.At the same time,the results suggested that excessive intake of fructose should be avoided when taking diet with high purine.