| Hyperuricemia is a disease of abnormal uric acid metabolism,which is mainly caused by abnormal purine metabolism and abnormal excretion of uric acid.In recent years,due to the substantial improvement of people’s material living standards and the continuation of unreasonable eating habits,the prevalence of hyperuricemia in China continues to rise,and now it has become the“fourth highest”disease.Hyperuricemia is usually closely related to many metabolic diseases,such as hypertension,diabetes,cardiovascular disease.Dioscin is a kind of steroidal saponins,which is the most abundant in Dioscoreaceae plants.Chinese medicine believes that dioscorea has a variety of effects,such as reducing swelling,eliminating phlegm,cutting malaria.,relaxing muscles,digesting food and diuresis,expelling phlegm,and intercepting malaria”.Modern studies have proved that dioscin has many pharmacological effects,such as anti-tumor,reducing blood lipid,improving cardiovascular function,and regulating immunity.Several studies have shown that dioscin could reduce the level of uric acid in blood.However,there is no study on the mechanism of diosgenin against hyperuricemia.In this study,metabonomics,lipidomics and transcriptomics techniques were used to comprehensively explore the metabolic pathways related to the effect of dioscin on hyperuricemia,and to screen the biomarkers and differential metabolic genes related to uric acid metabolism.The specific research contents and results are as follows:1.In this study,29 male Kunming mice were divided into potassium oxalate intragastric administration group(PO,200 mg/kg/d),dioscin group(potassium oxazinate+dioscin,200mg/kg/d and 50 mg/kg/d,respectively)and normal group(blank).All mice were treated by oral administration for 42 days.The model of hyperuricemia and the regulation effect on the PO group by dioscin were established.The serum uric acid value of mice was detected,the biological samples of experimental mice(blood sample,urine sample,liver and kidney)were collected,and histopathological analysis was also carried out.2.Based on ~1H-NMR and UHPLC-MS techniques,a method for the identification of metabolites in plasma and urine of mice was established.The differential metabolites related to hyperuricemia model and the dioscin in the treatment of hyperuricemia were characterized by metabonomic analysis,and 33 differential metabolites were screened.3.According to the results of metabonomics,it was found that some of the differential metabolites in plasma were lipids.Furthermore,targeted lipidomics was used to detect the lipid components in mice plasma by UHPLC-MS technology combined with schedule MRM mode,and the difference compounds between different groups were analyzed.A total of 19kinds of differential lipids related to the establishment of hyperuricemia model and dioscin treatment were explored.4.Based on transcriptomics,it was found that dioscin may improve the metabolic disorder caused by hyperuricemia through regulating the levels of six kinds of mRNA.The comprehensive analysis with the metabonomics and lipidomics provides clues for elucidating the mechanism of dioscin in reducing uric acid.Through the above analysis,it was found that differential metabolites were mainly involved in purine metabolism,tricarboxylic acid cycle,Synthesis and metabolism of amino acids,and lipid metabolism.Differential genes are mainly involved in cell cycle and energy metabolism.These metabolites and genes may provide useful information for further study of the therapeutic mechanism of dioscin as well as the early diagnosis of hyperuricemia. |
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