| BackgroundHyperuricermia is a metabolic disease in which serum uric acid content is increased due to disorders of purine metabolism in the blood of the body,excessive production of uric acid,and/or excretion disorders.In recent years,with the advent of an aging society,the continuous improvement of people's living standards,and the change in dietary habits,the incidence of hyperuricemia has gradually increased,and the age of onset has also shown a trend of rejuvenation.This is a huge burden on society and families,become one of the high incidence of the middle-aged and older men in the world today,especially in the coastal areas.Currently used for the treatment of hyperuricemia drugs,such as allopurinol,febuxostat,benzbromarone and colchicine,long-term use will bring serious side effects,and a certain degree of liver and kidney function damage.In recent years,Chinese medicine has achieved certain results in the clinical treatment and basic experimental research of hyperuricemia.It has unique advantages,and has become a hot spot in the study of hyperuricemia.The research group relied on the research of the National Natural Science Foundation of China's "Based on the P38-NF-?B-MCP-1 pathway study expelling stone,excreting water and eliminate blood stasis methods in protecting Vascular endothelial function of hyperuricemia rats".At the different levels of body,tissues,cells,and molecules,a large number of experimental studies were conducted on the effect of LishiHuoxue Fang on hyperuricemia model rats.The study found that LishiHuoxue Fang has the exact effect of lowering serum uric acid,aslo can protect the vasomotor function of the vascular endothelium and aortic morphology of experimental animals,reduce the inflammatory reaction of the kidney tissue,protect renal function,and by inhibiting P38-NF-?B-COX-2-MCP-1 pathway associated in:flammatory factors expression protects against vascular endothelial damage caused by hyperuricemia.Studies have found that about 90%of hyperuricemia develops due to reduced uric acid excretion.The excretion of uric acid is mainly dependent on the metabolic function of the kidney.There are many uric acid transporters that have reabsorption and secretion in the kidney.The action of this type of transporter to treat hyperuricemia has attracted more and more attention of researchers.The occurrence of hyperuricemia is closely related to the level of oxidative stress in the body.Under normal physiological conditions,uric acid can be used as the body's endogenous antioxidant substances,can react with a variety of oxidants and scavenge oxygen free radicals to inhibit oxidative stress damage;but in recent years,studies have shown that the ability of uric acid to scavenge oxygen free radicals is limited.The high uric acid level can reduce the antioxidant capacity of the body and promote the increase of oxidative stress damage.According to the multi-target effect of traditional Chinese medicine,based on the previous study of the study group,from the perspective of renal uric acid transporter and oxidative stress,the mechanism of action and anti-oxidation protective effect of LishiHuoxue Fang,which has the effects of clearing away heat and dampness,and promoting blood circulation,was in-depth explored.ObjectivesThis study was conducted to investigate the effects of different doses of LiShiHuoXue Fang on uric acid production,renal uric acid transporter and antioxidant capacity in rats with hyperuricemia caused by yeast paste and adenine supplementation,and to compare to traditional Chinese medicine with heat and dampness SiMiaoWan and western medicine clinical common drug benzbromarone,in-depth discussion of LiShiHuoXue Fang on the reduction of serum uric acid in rats with hyperuricemia and protective mechanism,with a view to the basic theory of traditional Chinese medicine treatment of hyperuricemia and clinical efficacy provides experimental evidence,and reveals the advantages and features of traditional Chinese medicine in the treatment of hyperuricemia.MethodsSD rats were randomly divided into blank group and modeling group according to body weight.In the modeling group,hyperuricemia rat models were prepared by continuous intragastric administration of yeast paste and adenine.After 14 days,the eyelids blood was used to test the hyperuricemia rat model.After the successful model examination,the modeling group rats were divided into model group,SiMiaoWan group,benzbromarone group,and high,medium,low dose groups of LiShiHuoXue Fang.Rats in each group were given intragastric administration of distilled water,SiMiaoWan,benzbromarone,LishiHuoxue Fang respectively for 14 days.1.On the 7th and 14th days after modeling,on the 7th day of administration,blood was collected from the orbital iliac veins and the level of SUA in each group was determined.After 2 hours of the last administration of gavage,the abdominal aorta was used to take blood,and the SUA level,the activity of XOD and ADA were measured.2.Metabolism cages were used to collect the 24h urine of rats on the administration of 13th to 14th day,and the levels of UV,UUA and UCr in each group were determined.Two hours after the last administration,blood was taken from the abdominal aorta,and the serum SCr and BUN level were determined in each group.The renal tissues were removed and the expressions of URAT1,MRP4,and ABCG2 proteins in kidney tissues of each group were detected by immunohistochemistry and Western blot.The level of gene expression of URAT1mRNA,MRP4mRNA,and ABCG2mRNA in kidney tissues of each group were detected by RT-PCR.3.After 2 hours of the last administration,blood was collected from the abdominal aorta.The serum activities of SOD,T-AOC,GSH-Px,CAT and the contents of MDA,ROS were determined.After the blood was taken from the abdominal aorta,the left kidney was removed and the homogenate was used to measure SOD,T-AOC activity and MDA content.Results1.After 14 days of yeast paste and adenine gavage,compared with the blank group,the level of SUA in the model group was significantly higher(P<0.001).Compared with the model,on the 14th day of administration,the level of SUA in the high and medium groups of LiShiHuoXue Fang was significantly reduced(P<0.01,P<0.05),and the LiShiHuoXue Fang high and medium groups XOD activity was significantly decreased(P<0.001,P<0.05),and ADA activity in the LiShiHuoXue Fang high group was decreased(P<0.01).2.Compared with the model group,the kidney index of the high and medium groups of LiShiHuoXue Fang was significantly lower(P<0.01,P<0.05).the level of UUA and 24hUUA in the group of LiShiHuoXue Fang high group was significantly higher(P<0.05),and the level of UCr in the group with the LiShiHuoXue Fang high and medium groups was increased(P<0.001,P<0.05),SCr level of high and medium LiShiHuoXue Fang groups was decreased(P<0.01,P<0.05),the level of BUN of high and medium LiShiHuoXue Fang groups decreased(P<0.05).Compared with the model group,the immunohistochemical method showed that the LiShiHuoXue Fang high group can reduce the expression of URAT1 protein and increase the protein expression of MRP4 and ABCG2 in the kidney(P<0.001,P<0.05?P<0.01).Western Blot assay showed that the LiShiHuoXue Fang high group can reduce the expression of URAT1 protein and increase the protein expression of MRP4 and ABCG2 in the kidney(P<0.01,P<0.05,P<0.01).The results of RT-PCR showed that the LiShiHuoXue Fang high group can reduce the gene expression of URAT1mRNA and increase the gene expression of MRP4mRNA and ABCG2mRNA in the kidney(P<0.05,P<0.05,P<0.05).3.Compared with the model group,the SOD activity in the serum of high,medium and low of LiShiHuoXue Fang groups was significantly increased(P<0.01,P<0.05,P<0.05).Serum T-AOC activity was significantly increased in high and medium of LiShiHuoXue Fang groups(P<0.05,P<0.05),and the MDA content in the serum of LiShiHuoXue Fang high group was significantly decreased(P<0.05).The serum ROS levels of the high and medium LiShiHuoXue Fang groups were decreased(P<0.01,P<0.05).Compared with the model group,the activity of SOD in the kidney of the group treated with LiShiHuoXue Fang high was significantly increased(P<0.001).The activity of T-AOC in the kidney of LiShiHuoXue Fang high group was significantly increased(P<0.05).The MDA content in kidney of the high LiShiHuoXue Fang group was significantly reduced(P<0.05).Conclusions1.LiSliiHuoXue Fang can effectively reduce the SUA level in hyperuricemia model rats,which may relevant to reduce the serum XOD,AD A enzyme activity,reduce the decomposition of xanthine,so that the uric acid generated by hyperuricemia model rats reduce.2.LiShiHuoXue Fang can effectively increase the level of UUA excretion in hyperuricemia model rats,increase the excretion of UCr,and can reduce the kidney index,which has a significant down-regulation of SCr and BUN levels,indicating that the decoction is promoting uric acid excretion also has a protective effect on kidney function.LiShiHuoXue Fang can inhibit the expression of URAT1 protein and URAT1mRNA in hyperuricemia model rats and upregulating the expression of MRP4 and ABCG2 proteins and MRP4mRNA and ABCG2mRNA,to reduce the reabsorption of uric acid in renal proximal tubules and promote uric acid excretion,to reduce the body's serum uric acid levels.3.LiShiHuoXue Fang can enhance the activities of SOD and T-AOC in serum and kidney tissues,reduce the content of MDA in serum and kidney tissues,and decrease the serum ROS level,indicating that LiShiHuoXue Fang can enhance the activity of antioxidant enzymes,strengthen the body's ability to scavenge oxygen free radicals,reduce lipid peroxidation damage,reduce the content of lipid oxidation metabolites,and have the effect of enhancing the antioxidant capacity of hyperuricemia model rats,and may improve the anti-oxidation ability of kidney tissue to play its role in the protection of renal tissue function,to a certain extent,to reduce the oxidative damage of the kidney tissue,so that it can normally play a role in metabolism,promote the excretion of uric acid in the body.In summary,this study has revealed through experimental research that the traditional Chinese medicine compound prescription LiShiHuoXue Fang,which is mainly produced by heat-clearing,dampness-removing,blood-activating and stasis-resolving methods,can reduce serum XOD and ADA enzyme activity,and can inhibit the expression of URAT1 protein and URAT1mRNA in rat kidney,upregulated the expression of MRP4,ABCG2 protein and MRP4mRNA,ABCG2mRNA to increase the excretion of uric acid,to make the role of reducing uric acid level in hyperuricemia rats.Then,to a certain extent the serum and kidney antioxidant enzymes can be increased,reduce lipid peroxidation damage,to enhance the antioxidant capacity of hyperuricemia rats,and have a certain degree of protection of renal function.LiShiHuoXue Fang plays a comprehensive therapeutic effect on hyperuricemia. |
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