The Study Of Uric Acid On Lowering Effects And Underlying Mechanisms Of Baicalin On Hypertension

Aims:Based on prophase experiments,further studies are performed to examine the effects of Baicalin on metabolic disorders in hypertension,especially about uric acid lowering effects and related underlying mechanism.It will provide certain experimental evidence for the clinical applications of Baikal skullcap root.Methods:1.Spontaneously hypertensive rats of 6 weeks old were randomly grouped as Vehicle control and Baicalin treatment.The equivalent Wistar-Kyoto rats were grouped as normal control.About 5-week intervention,serum untargeted metabolomics were used to study the regulating acts of Bai on metabolic disorders in SHR.2.Uric acid(UA)assay kit was performed to detect the levels of uric acid from each group.3.Xanthine oxidase(XOD)activity assay kit was performed to detect XOD activity in above rats' livers.4.Real time-Polymerase Chain Reaction(PCR)was used to analyze the mRNA expression levels of certain uric acid transporter genes in above rats' livers,kidneys and ileums.Results:1.In the serum untargeted metabolomics report,differential metabolites between SHR_Vehicle group and WKY group were shown.Among them,uric acid was significantly increased in SHR_Vehicle group(VIP>1,P<0.05,FC>1),comparing with WKY_Vehicle group.It was significantly decreased in SHR_Baicalin group(VIP>1,P<0.05,FC<1).2.The quantitative analysis of serum uric acid indicated thatno significance differ in SHR group and WKY group when 4 weeks old and 6 weeks old(P>0.05),SUA of SHR group was significantly higher than that of WKY group when 8 weeks old(P<0.05).After treatment of Baicalin acting on SHRs of 6 weeks old and 26 weeks old,SUA of these two groups were both significantly decreased(P<0.05).It revealed that Baicalin may take the protection and treatment effect on elevated SUA in SHRs.3.(1)The analysis of XOD activity indicated that of SHR_Vehicle group was significantly higher than XOD activity of WKY_Vehicle group(P<0.05).Compared with SHR_Vehicle group,XOD activity of SHR_Baicalin group was significantly reduced(P<0.05).It revealed that Baicalin may act as inhibitor of uric acid synthesis in SHRs.(2)The result of mRNA expression levels of certain uric acid transporter genes indicated that some uric acid transporter genes on livers,kidneys and ileums in SHR-Vehicle group express differentially,compared with those in WKY_Vehicle group(P<0.05).In SHR_Baicalin group,the expression level of Kidney GLUT9 was significantly decreased(P<0.05),the expression level of Kidney UAT and Ileum GLUT 9 were significantly increased(P<0.05),however there were no significance in the expression level of Liver GLUT9,Kidney URAT1,Kidney MRP4,Kidney ABCG2,Kidney OAT 1 and Ileum ABCG2(P>0.05).Conclusions:1.The trend of serum uric acid level is consistent with blood pressure increasing in SHRs,and it suggested that elevated uric acid level may result from enhanced XOD activity and changes of uric acid transporter(GLUT9 and UAT)expression.2.Baicalin could significantly protect and treat increased uric acid level in SHRs.3.Baicalin could lower uric acid level in SHRs,and it could be related to inhibiting XOD activity,elevated expression level of Kidney UAT and Ileum GLUT 9 and decreased expression level of Kidney GLUT9.4.Baicalin may play the partial role as uricosuric agent and uric acid reabsorption inhibitor in kidney during hypertension.