天麻素对次黄嘌呤诱导小鼠急性高尿酸血症的影响和机制研究

Study of the effects and mechanisms of gastrodin on acute hyperuricemia of mice induced by hypoxanthine

目的探讨天麻素(GAS)对次黄嘌呤诱导的小鼠急性高尿酸血症(HUA)的影响及可能机制。方法雄性昆明种小鼠50只随机分为5组,分别为正常组、模型组、GAS 200 mg/kg组、GAS 400 mg/kg组和别嘌呤醇(ALLO)10 mg/kg组,每组10只。灌胃给药14 d,于末次给药1 h后除正常组外其余各组动物腹腔注射次黄嘌呤1000 mg/kg。注射45 min后取血测定血清生化指标。动物处死后取肝脏以试剂盒测定黄嘌呤氧化酶(XOD)活力,并取肾脏提取RNA,反转录后以实时荧光定量PCR检测尿酸盐转运蛋白1(URAT1)和有机阴离子转运蛋白1(OAT1)的mRNA表达水平。结果模型组动物血清尿酸(UA)水平和肝脏XOD活力高于正常组,肾脏URAT1的mRNA表达水平高于正常组,而OAT1的mRNA表达水平低于正常组,差异有统计学意义(P<0.01或P<0.001)。剂量为200 mg/kg和400 mg/kg的GAS使小鼠血清UA水平下降,同时使肝脏XOD活力减少,肾脏URAT1的mRNA表达水平下降而OAT1的mRNA表达水平增加(与模型组比较,P<0.05或P<0.01)。ALLO使上述指标均恢复正常(与模型组比较,P<0.01或P<0.001)。结论GAS可能通过抑制肝脏XOD活力、下调肾脏URAT1的mRNA表达和上调肾脏OAT1的mRNA表达来改善次黄嘌呤诱导的小鼠急性HUA。

Objective To study the effects and possible mechanisms of gastrodin(GAS)on acute hyperuricemia(HUA)of mice induced by hypoxanthine.Methods A total of 50 male Kunming mice were randomly divided into five groups,which included the normal group,the model group,GAS 200 mg/kg group,GAS 400 mg/kg group,and allopurinol(ALLO)10 mg/kg group.There were 10 mice in each group,and the drugs were intragastricaly administered for 14 days.One hour after the last drug administration,mice were intraperitoneally injected with hypoxanthine at a dose of 1000 mg/kg,except for the normal group.Blood samples were collected for the assay of serum biochemical parameters 45 minutes after the injection.The animals were then sacrificed,and their livers were harvested for the determination of xanthine oxidase(XOD)activity by a kit.The kidneys were also collected for RNA extraction,and after reverse transcription,the mRNA expression levels of urate transporter 1(URAT1)and organic anion transporter 1(OAT1)were determined by quantitative real-time PCR.Results The serum uric acid(UA)level and liver XOD activity of the model group were higher than that of the normal group,the mRNA expression level of URAT1 in the kidney was higher than that of the normal group,while the mRNA expression level of OAT1 was lower than that of the normal group,the differences were statistically significant(P<0.01 or P<0.001).Administration of 200 mg/kg and 400 mg/kg of GAS decreased serum UA of the mice.Meanwhile,they also reduced liver XOD activity,decreased renal URAT1 mRNA expression level and increased that of OAT1(P<0.05 or P<0.01 compared to model group).ALLO restored the above parameters to normal(P<0.01 or P<0.001 compared to model group).Conclusion GAS improves acute HUA of mice induced by hypoxanthine,which may be attributable to inhibition of liver XOD activity,down-regulation of renal URAT1 mRNA expression,and up-regulation of renal OAT1 mRNA expression.