茶黄素降低高尿酸血症小鼠血清尿酸的作用与机制探究

Mechanism and uric acid reducing effects of theaflavin on potassium oxonate-induced hyperuricemia in mice

目的:研究茶黄素对氧嗪酸钾诱导的小鼠高尿酸血症的治疗作用与机制探究。方法:将小鼠随机分为对照组、模型组、茶黄素低、中、高组,阳性药别嘌呤醇和苯溴马隆组,氧嗪酸钾300 mg·kg^(-1)每日腹腔注射(ip)诱导小鼠高尿酸血症模型,造模成功后灌胃(ig)给药2周,末次给药后取小鼠血清、肾脏、肝脏,测定血清中尿酸(UA)、尿素氮(BUN)、肌酐(CRE)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、低密度脂蛋白(LDL)、胆固醇(CHO)水平;并用苏木素-伊红(HE)染色处理肾脏组织切片,光镜观察病理学改变;试剂盒测定肝脏黄嘌呤氧化酶(XOD)活力;实时荧光定量聚合酶链式反应qRT-PCR测定肾脏与尿酸合成与排泄相关基因的mRNA表达。Western Bolt测定肾脏尿酸盐转运体URAT1与有机阴离子转运体OAT1蛋白的表达情况。结果:在氧嗪酸钾诱导的小鼠高尿酸血症模型中,茶黄素(10 mg·kg^(-1),ig)可明显降低血清尿酸水平与LDL水平;相比别嘌醇,对肾脏并无明显损伤作用;茶黄素分别能升高NPT4,GLUT9,URAT1的mRNA表达水平,可降低OAT1,OAT2,PDZK1表达;茶黄素可增加GLUT9蛋白表达。结论:茶黄素可降低高尿酸血症小鼠血清尿酸。其降低血清尿酸作用与抑制黄嘌呤氧化酶活性、调节相关阴离子转运体mRNA与蛋白表达水平相关。

Objective： To study the effect of theaflavin on potassium oxonate-induced hyperuricemia in mice and the related mechanism. Methods： Mice were randomly grouped as control,model,theaflavin low dose,middle dose,high dose,allopurinol,and benzbromarone groups. Hyperuricemia model was built by 300 mg·kg^（-1） potassium oxonate given by intraperitoneal injection. After model establishment,theaflavin was administered for two weeks,and serum,kidney,ileum and liver samples were taken. UA,BUN,CRE,ALT,AST,LDL,and CHO were assayed by biochemical analyzer. The tissue of kidney was observed after HE staining. XOD activity was assayed by testing kit. The expression of genes that are related to uric acid synthesis and excretion was determined by qRT-PCR. The expression of transport protein URAT1,GLUT9,ABCG2 and OAT1 was measured by western blot.Results： Theaflavin of 10 mg·kg^（-1） could significantly reduce the serum uric acid level. Compared with allopurinol,theaflavin had less damage to kidneys. Theaflavin could increase the expression of mRNA of URAT1,GLUT9 and NPT4. Meanwhile it could reduce the expression of mRNA of OAT1,OAT2,PDZK1. Theaflavin could increase theexpression of GLUT9 transporter. Conclusion： Theaflavin can reduce the serum uric acid level in hyperuricemia mice,which may be related to its effects on the mRNA and protein expression of anionic transporter.