Establishment And Application Of A Screening System For Anti-hyperuricemia Drug

Hyperuricemia(HUA)is one of the metabolic diseases,caus by purine metabolic disorder.It is not only the direct risk of gout,but also is closely related to metabolic syndrome,chronic kidney disease,and cardiovascular disease.For the prevention and treatment of these diseases,the control of blood uric acid in those patients with hyperuricemia is becoming more and more attentions.In clinical,the drugs for the treatment of hyperuricemia are still relatively deficient,and can't meet the demand.It is urgent to develop new drugs.But,the technique for screening is ungratified.In the methods of xanthine oxidoreductase(XOD)inhibitor screening in vitro,it is easily to show false negatives or false-positive results because the diverse source XOD enzymes.In the animal models of hyperuricemia,the insufficient maintenance of serum uric acid is the common problem.In this study,firstly,the more refined XOD inhibitor screening model is established with the milk source XOD1(PDB ID:3AMZ)in vitro.Utilizing this model,20 samples,which significiantly inhibited XOD activity,are found from 1566 compounds.Sondly,acute hyperuricemia mouse model is established by single-dose stimulation of both potassium ozonate(OXO)and hypoxanthine(HA)in ICR mice;and the XOD activity,liver and kidney function were investgated;then,the effects of 9 samples on transient hyperuricemia were screened,respectively.Finally,chronic hyperuricemia mouse model is established by administration OXO for 14 days in ICR mice;and the harm of liver and kidney,and the changes of liver and serum XOD activities were observed;then,the effects of 4 compounds on hyperuricemia were studied.In conclusion,the anti-hyperuricemia drug screening system is set up in vivo and in vitro,which will lay an experimental foundation for the development on anti-hyperuricemia drugs.