The Effects Of Vitamins B On Mice Hyperuricemia

Background:Hyperuricemia not only is an independent risk factor to cardiovascular disease,but also a strong predictor in both the mortality of patients with heart failure and coronary heart disease and the incidence of cardiovascular events in diabetic patients. Endothelial dysfunction,caused by hyperuricemia,is closely related to the occurrence and development of cardiovascular diseases,such as hypertension,coronary heart disease and heart failure.At present,there is not a generally accepted animal model of an ideal,and the conventional drugs,including benzbromarone,probenecid,allopurinol,etc.,of which side effects can not be ignored.Objective:We construct a mouse model of hyperuricemia,observe the role of vitamins B in hyperuricemia mice to study its effectiveness and mechanism of lowering uric acid and to find a new way to lower uric acid;At the same time we are to study the role of vitamins B about vascular endothelial,for further explore the mechanism of uric acid causing endothelial dysfunction.Methods:1.To construct a mouse model of hyperuricemia.52 SPF-class male mice were completely randomly divided into 4 groups:C group(control group),M1 group,M2 group and B group,in which distilled water administered to C group,Yeast extract to the M1 group,Ethambutol + Yeast extract to the M2 group,B group administered for Yeast extract + Ethambutol + Allopurinol tablets,3 weeks later,all mice were weighed,picked eyes to get blood,and measured serum uric acid level.2.Observationg of the role of vitamins B.72 SPF-class male Kunming mice were randomly divided into 6 groups completely,C group(control group),M group,B group,V1 group,V2 Group,V3 group.With the exception of the control group,mixed solution of Yeast extract + Ethambutol was given to the remaining groups,besides,group B added with Allopurinol tablets,V1 group,V2 Group and V3 group was added with low -dose,mid-dose and high -dose folic acid +VB₆ +VB₁₂ mixed solution separately.3 weeks later,all mice weighed,picked eyes to get blood,measured serum uric acid and serum NO,then separated thoracic aorta,sections for HE staining and detection of the expression of NF-κB with immunohistochemical methods.Results:1.The serum uric acid level of M2 group was significantly higher than the level of C group and M1 group(P <0.01).B group was significantly lower than the M2 group in the level of serum uric acid(P <0.01).2.The serum uric acid level of vitamins groups (V1 group,V2 Group and V3 group) were lower than that of Yeast extract + Ethambutol group(M group)(P < 0.01),and high-dose vitamins group(V3 group) to decline in the level of uric acid becomes more apparent(compared with C group P <0.05).3.The serum NO level in V2 Group and theV3 group were significantly higher than in M group(P <0.01).The serum NO levels of B group was significantly lower than the level of V2 and V3 group(P< 0.05).The serum NO level in V2 and V3 were not different with the control group(C group)(P> 0.05).4.The serum NO level was negatively correlated with the serum uric acid level(r =-0.278,P <0.05).5.NF-κB of aorta in the M group showed positive expression,B group and V1 group showed weak positive expression,V2,V3 and C groups did not express.6.All aortic intima HE staining patterns did not apear to change.Conclusion:1.Intragastric administration of Yeast extract + Ethambutol in mice can establish a stable model of hyperuricemia,and continuous feeding for three weeks has managed to maintain a high level of serum uric acid,significantly better than oral Yeast extract simply.2.Folic acid+vitamin B₆ +vitamin B₁₂,including high-dose group, mid-dose group and low-dose group,can effectively reduce serum uric acid levels of hyperuricemia mice,which appears to dose-dependent manner.3.Larger dose of folic acid+vitamin B₆ +vitamin B₁₂ effectively reverses the dysfunction of endothelial cells by hyperuricemia,which is manifested as increased serum levels of NO.4.Folic acid can inhibitor endothelial NF-κB positive expression.