Isolation Of Hypouricemic Probiotics And Exploration The Mechanism Of Hyperuricemic Effects On Model Rats

Hyperuricemia is defined as a kind of metabolic disease with significant higher blood uric acid level than normal under normal diet.The clinical diagnostic indicator for hyperuricemia is as followed: more than 420 ?mol/L serum uric acid for male and 357 ?mol/L for female.It is reported that hyperuricemia can not only deteriorate into gout,and but also is treated as a dangerous factor for arteriosclerosis,hypertension,insulin resistance and so on.Drugs for hyperuricemia usually have strong side effects and low tolerance to patients.It is becoming a new method for treating hyperuricemia by indirectly degrading exogenous purine compounds ingested from food through Lactobacillus.The aim of this study was to select hypouricemic probiotics from 30 candidate strains and explore its mechanism on hyperuricemic rats.First of all,through the co-culture between probiotics and the phosphate buffer that contains uric acid,purine(xanthine,xanthine,guanine),nucleosides(adenosine,guanosine),nucleotides(adenosine monophosphate,guanosine monophosphate),HPLC was used to evaluate the abilities of probiotics to degrade uric acid,purine,nucleotides and nucleosides.The best probiotics were selected and verified by hyperuricemia rat model.Extracellular secretions and cell-free extracts of ZM15 were tested whether having ability of degrading nucleosides and nucleotides with HPLC.The changes of key metabolites in the process of ZM15 degrading nucleosides and nucleotides were monitored by HPLC-Triple Quadrupole Mass(QQQ).In the end,the mechanism of ZM15 lowering the blood uric acid was initially preliminarily explored.The results of HPLC showed that lactobacillus casei ZM15 has the strongest ability of degrading nucleosides and nucleotides among 30 different probiotic strains.ZM15 cell-free extracts can degrade both nucleosides and nucleotides,but the extracellular secretions can't,which indicates the degrading process exists in cell.The results of mass spectra showed that in the process of ZM15 degrading nucleosides and nucleotides,xanthine,hypoxanthine and guanine appeared both outside and inside cells,the content of three purines in the cell were significantly higher than that inside normal cell,uric acid and allantoin were not detected.The decrease of serum uric acid levels in hyperuricemic rats was detected after treatment of ZM15 for 1-2 weeks,which indicate ZM15 has the effect of lowering blood uric acid.Lactobacillus casei ZM15 with the abilities of degrading nucleosides and nucleotides can reduce the level of blood uric acid mainly by competing with human intestinal epithelial cells to absorb nucleoside and nucleoside.