The Cloth Sutent Of High Uric Acid Hematic Disease Renal Uric Acid Salt Transporters Control Mice

Research backgroud and purposeIn China,with rapid and lasting growing of economy,people’s living standard has been greatly improved,and daily eating habits change accordingly.Daily intake of high fat,high calorie,and high purine content of food increases.Therefore,hyperuricemia incidence is increasing whichhas seriously affected people’s work and life,threating human health.Therefore,more medical professionals are attracted to explore its causes,seeking the methods of prevention and treatment.With the development of molecular biology,the pathogenesis of hyperuricemia are aware increasingly,and all kinds of transporters and targets are being found constantly.Uric acid anion transporter(URAT1)、organic cation transporter(OCTs)、organic cation/carnitine transporter(OCTNs)、organic anion transporter(OAT)Uric acid salt of rotating body are found,which plays an important role in constant development of new drugs to treat hyperuricemia.As a new kind of medicine to treat hyperuricemia,febuxostat was approved in February 2009 by the US Food and Drug Administration(FDA)in the treatment of hyperuricaemia and gout patients,is a highly selective inhibitor of xanthine oxidase(XO),andinhibitory effect of specificity for reduced and oxidized XO were significant.The mechanism of its action combines with molybdenum pterin active site,stopping XO on molybdenum pterin to combine with the substrate binding,thus suppressing generation of uric acid.Therefore,this paper is to provide the experimental basis for further related research in the sick condition of mice abdominal injection of potassium oxonate induced hyperuricemic,the influence of febuxostat on hyperuricemia in mice pathological state and whether its mechanism is related to URAT1,OCT2,and OCTN2.MethodsTo establish the mice model of hyperuricemia with potassium oxonate by i.p..KM male mice were randomly divided into 6 groups,12 rats in each group.They are normal group,model group,positive control group,low,middle,high dose of febuxostat groups.Renal pathological changes were observed by HE staining,the determination of serum uric acid,creatinine and urea nitrogen levels in mice according to the kit instructions,and the expression of URAT1,OCT2,OCTN2 protein is determined by Western blot.Results(1)Mice serum uric acid,urea nitrogen,creatinine levels in Hyperuricemia mice model group were significantly higher than those in the normal group(P<0.05)Compared with the model group,the positive control group,high dose group,and febuxostat group,uric acid levels decreased significantly(P<0.01),uric acid levels decreased in the low dose group of(P<0.05);and creatinine levels decreased significantly in the positive control group,low,middle and high dose group,blood urea nitrogen(P<0.05).(2)In terms of kidney morphology,compared with the normal group,hyperuricemia model mice glomerular mesangial cells and matrix are severe hyperplasia,with more inflammatory cell infiltration,changing renal tubular epithelial cells shedding,necrosis;febuxostat dose group can decrease kidney tissue injury in mice,and infiltration of inflammatory cells were significantly less than the model group mice,only a few is inflammatorily invaded.The degree of lesion is the lightest in febuxostat middle dose group and febuxostat high dose group.(3)URAT1 protein expression significantly increased in hyperuricemia mice model group(P<0.01),OCT2,OCTN2 protein expressionwas significantly decreased(P<0.01);Compared with the model group,theprotein expression was significantly decreased,OCT2 protein expression was significantly increased renal expression of URAT1 protein in the positive control group(P<0.01),the expression of OCTN2 protein was significantly increased(P<0.05),the expression of febuxostat low dose group of mouse renal URAT1 protein was decreased obviously,the renal expression of OCT2 protein was significantly rise(P<0.05),the expression of OCTN2 protein was significantly increased(P<0.01);in the high dose group of febuxostat,renal URAT1 protein in miceexpression was decreased significantly(P<0.01),renal OCT2,OCTN2 protein expression was significantly increased(P<0.01).Conclusion(1)Potassium oxonate inducing hyperuricemic mice can increase the levels of uric acid in mice,and febuxostat can decrease uric acid.(2)In the process of the formation of mice hyperuricemia,the kidney URAT1 protein express elevates,and expression of OCT2,OCTN2 transporter reduces.Febuxostat could reduce the level of uric acid in mice by regulating URAT1,OCT2,and OCTN2 protein.