Uric Acid Distribution In Uox^-/- Rats’ Tissues And Their Biological Evaluation

Objectives:The project is to detect the uric acid level in various tissues and intestinal juice of uricase-deficient(Uox^-/-)rats.The blood biochemical indexes were analyzed to provide a reliable basic data for the ideal animal model of gout and hyperuricemia（HUA）prevention and treatment.Methods:1.We examined the uric acid level in various tissues of two groups’Uox^-/-rats:10 male Uox^-/-rats of 2-month’s old and 10 male Uox^-/-rats of 11-month’s old.Their intestinal juice,blood,heart,liver,spleen,lung,kidney,and other tissues were collected to evaluate the uric acid concentration.We determined the pH value in intestinal fluid and analyzed the correlation between pH value and the uric acid level.The uricase activity in rats was detected by a microplate reader.At the moment,we detected the mRNA expression levels encoding urate transporters and other proteins by high-throughput sequencing,including xanthine dehydrogenase（Xdh）,adenosine deaminase（Ada）,URAT1（Slc22al2）,GLUT9（Slc2a9）,OAT10（Slc22al3）,BCRP（Abcg2）,OAT1（Slc22a6）,OAT3（Slc22a8）,UAT（Lgals9）,and sodium phosphate transporters NPT1（Slc17a1）and NPT4（Slc17a3）.2.We examined the liver function indexes,renal function indexes,glucose and lipid metabolism indexes to estimate rats’ hepatic and kidney function.The rats’pathological damage was analyzed by routine histopathological examination.Results:1.Compared with SD rats,the SUA level in Uox^-/-rats was significantly higher,with an average of 62.77 μg/ml.In addition,the uric acid level in organs of Uox^-/-rats is higher than that of the wild-type rats,and the uric acid level in older rats was the highest.The concentration of uric acid in the adrenal gland,duodenum,liver,kidney,and ileum was higher than that in other tissues.The pH value in intestinal juice was similar to but lower than that of SD rats’ each segment.There was no uricase activity in Uox^-/-rats.The mRNA expression of enzymes and urate transporters,including Xdh and Ada in the liver,URAT1,OAT 10,UAT,and Abcg2 in the kidney was significantly down-regulated,and the mRNA expression of OAT3 and NPT1 was significantly up-regulated in the older rats（P<0.05）.2.The hepatic function indexes were in the normal ranges.However,compared with SD rats,the blood creatinine,blood urea nitrogen,glucose,and low-density lipoprotein cholesterol content of the older rats significantly increased,while the high-density lipoprotein cholesterol content decreased.The kidney and lung tissues were mildly injured.Conclusion:Compared with wild-type SD rats,Uox^-/-rats have higher SUA with the average of 62.77 μg/ml and the uric acid in Uox^-/-rats’ tissues is also higher than that in wild-type SD rats.The high distribution of uric acid in young Uox^-/-rats’tissues is the adrenal,duodenum,lung,spleen,ileum and kidney in the order,and the older Uox^-/-rats have more uric acid in their ileum and spleen than younger rats.The skeletal muscle and brain tissues have the lest level of uric acid.The mRNA expression of urate-related enzymes and transporters in Uox^-/-rats is altered,URAT1 and OAT 10,the transporters associate with urate reabsorption in kidney,and Abcg2 that relates to urate excretion in ileum are down-regulated.The kidney is damaged by the increase of uric acid level,and the glucolipid metabolism of the older Uox^-/-rats is abnormal.