The Preventive Effect And Mechanism Of Yi-suan-cha On Hyperuricemia Rats

BACKGROUND AND OBJECTIVE: Hyperuricemia is a disease caused by the disorder of purine metabolism or uric acid excretion in the body,which results in the blood uric acid level exceeding the normal range.At present,the incidence of hyperuricemia in various regions is increasing year by year.However,the treatment of hyperuricemia requires long-term drug use,which is prone to recurrence.Long-term use of XOD inhibitors such as allopurinol will increase the risk of adverse reactions such as hepatotoxicity and renal toxicity.Therefore,searching for natural medicinal plants which have little side effects and are suitable for patients with gout and hyperuricemia is one of the hotspots of current medical research.The Yi-Suan-Cha is a kind of mixed tea preparation prepared by soaking,cooking,filtering and concentrating hawthorn leaves:Astragalus membranaceus: locust flower = 2:1:1 ratio.The aim of this study was to evaluate the hypouric acid effect of Yi-Suan-Cha on hyperuricemia rats and to explore the mechanism of hypouric acid.METHODS: According to the principle of random allocation,48 male SD rats were divided into normal control group,model group,allopurinol group,benzbromarone group,low-doseYi-Suan-Cha group and high-dose Yi-Suan-Cha group,with 8 rats in each group.The rat model of hyperuricemia wasestablished by intragastric administration of adenine 25mg/Kg + potassium oxalate 300mg/kg for 3 weeks.After the last administration,the levels of serum uric acid,creatinine and urea nitrogen were measured.The degree of renal pathological damage was observed by pathological section staining.Xanthine oxidase in serum and liver homogenate was measured by ELISA.The expressions of URAT1,ABCG2,OAT1,GLUT9 protein and mRNA in kidney were detected by Western Blot and RT-PCR,respectively.RESULT: 1.To detect the effect of Yi-Suan-Cha on serum uric acid,Cr and BUN levels in hyperuricemia rats,the results showed that compared with the normal control group,the level of uric acid in model group increased significantly(P < 0.05),suggesting that the model of hyperuricemia rats was established successful;Compared with model group,the level of serum uric acid in each medication group was significantly decreased(P < 0.05).Compared with the normal control group,the serum levels of Cr and BUN in the model group increased significantly,and the levels of Cr and BUN could not be decreased in each group.2.To detect the effect of Yi-Suan-Cha on renal histopathology in hyperuricemia rats,the results showed that the structure of glomeruli and tubules in the kidneys of rats in the normal control group was intact.In the model and the allopurinol group,the renal tubules showed shedding necrosis.The morphological structure of the benzbromarone,Yi-Suan-Cha low dose and Yi-Suan-Cha high dose groups was clear,and there was no obvious abnormality.3.The effect of Yi-Suan-Cha on XOD activity of rat serum and liver homogenate was tested,the results showed that compared with model group,the XOD activity of liver homogenate in allopurinol group was decreased.However,benzbromarone,low-dose Yi-Suan-Cha and high-dose Yi-Suan-Cha could not reduce the XOD activity of serum and liver homogenate.4.Western blot assay showed that compared with normal control group,the expression of URAT1 and GLUT9 protein were increased and ABCG2 and OAT1 protein were decreased in model group.Compared with the model group,the expression of URAT1 and GLUT9 protein in low-dose and high-dose Yi-Suan-Cha groups were decreased,while the expression of ABCG2 and OAT1 protein were increased.(P < 0.05).5.RT-PCR was used to detect the effect of Yi-Suan-Cha on the gene expression of transporter.The results showed that compared with the normal control group,URAT1 and GLUT9 mRNA were increased in the model group.Compared with the model group,URAT1 and GLUT9 mRNA were decreased in low-dose Yi-Suan-Cha group and high-dose Yi-Suan-Cha group,while ABCG2 and OAT1 mRNA were increased.(P < 0.05).CONCLUSION: 1.Yi-Suan-Cha can significantly reduce the serum uric acid level of hyperuricemia rats that induced by adenine 25 mg/Kg + potassium oxalate 300 mg/kg dosage for 3 weeks,and reduce the damage of kidney tissue.2.The down-regulation of URAT1,GLUT9 and the up-regulation of ABCG2,OAT1 may be one of the effective mechanisms of Yi-Suan-Cha in the treatment of hyperuricemia.