藏党参提取物对酵母膏联合氧嗪酸钾致高尿酸血症小鼠的保护作用研究

Study on the Protective Effect of Zangdangshen[Codonopsis thalictrifolia Wall.var.mollis(Chipp.)L.T.Shen]Extract on Hyperuricemia Mice Induced by Yeast Extract Paste Combined with Potassium Oxonate

目的:探究藏党参提取物对酵母膏联合氧嗪酸钾诱导的高尿酸血症小鼠的治疗作用及保护机制。方法:将60只雄性昆明种小鼠按随机数字表法分为空白组、模型组、藏党参提取物低剂量组、藏党参提取物中剂量组、藏党参提取物高剂量组、别嘌醇组,每组10只。除空白组外,其余小鼠每日灌胃给予酵母膏,持续14 d。在造模同时,各给药组分别给予相应药物。末次给药后,腹腔注射氧嗪酸钾(300 mg/kg)诱导小鼠高尿酸血症,检测小鼠肝脏指数和肾脏指数,检测血尿酸(SUA)、血尿素氮(BUN)、血肌酐(SCr)、尿尿酸(UUA)、尿尿素氮(UUN)、尿肌酐(UCr)水平;检测肝脏和血清中黄嘌呤氧化酶(XOD)、血清谷草转氨酶(AST)、血清谷丙转氨酶(ALT)活性及尿酸排泄分数(FEUA)。Western blotting法检测肾脏中尿酸盐转运蛋白1(URAT1)、葡萄糖转运蛋白9(GLUT9)、有机阴离子转运蛋白1(OAT1)、有机阴离子转运蛋白3(OAT3)蛋白表达水平。结果:与模型组比较,别嘌醇和藏党参提取物能显著改善小鼠肝脏指数,降低小鼠SUA、BUN及SCr水平,同时升高小鼠UUA、UUN及UCr水平,改善小鼠FEUA水平,抑制肝脏与血清中XOD和血清AST、ALT活性,下调肾脏中URAT1与GLUT9蛋白表达水平及升高OAT1与OAT3蛋白表达水平。结论:藏党参提取物对酵母膏联合氧嗪酸钾诱导的高尿酸血症小鼠具有保护作用,其机制可能是通过抑制XOD活性及调控尿酸转运体发挥作用。

Objective:To explore the therapeutic effect and protective mechanism of Zangdangshen[Codonopsis thalictrifolia Wall.var.mollis(Chipp.)L.T.Shen]extract on hyperuricemia mice induced by yeast extract paste combined with potassium oxonate.Methods:A total of 60 male Kunming mice were randomly divided into blank group,model group,Zangdangshen low dose group,Zangdangshen middle dose group,Zangdangshen high dose group and allopurinol group,with 10 mice in each group.Except the blank group,other mice were given yeast extract paste by gavage every day for 14 days.At the same time of modeling,each administration group was given corresponding drugs.After the last administration,potassium oxonate(300 mg/kg)was injected intraperitoneally to induce hyperuricemia in mice.The liver index and kidney index of mice were detected,and the levels of serum uric acid(SUA),blood urea nitrogen(BUN),serum creatinine(SCr),urine uric acid(UUA),urine urea nitrogen(UUN)and urine creatinine(UCr)were detected.The activities of xanthine oxidase(XOD)in liver and serum,serum aspartate aminotransferase(AST),serum alanine aminotransferase(ALT)and fractional excretion of uric acid(FEUA)were detected.The expression levels of urate transporter 1(URAT1),glucose transporter 9(GLUT9),organic anion transporter 1(OAT1)and organic anion transporter 3(OAT3)in kidney were detected by Western blotting.Results:Compared with the model group,allopurinol and Zangdangshen[Codonopsis thalictrifolia Wall.var.mollis(Chipp.)L.T.Shen]extract could significantly improve the liver index of mice,reduce the levels of SUA,BUN and SCr in mice,increase the levels of UUA,UUN and UCr in mice,improve the level of FEUA in mice,inhibit the activities of XOD in liver and serum,AST and ALT in serum,down-regulate the expression levels of URAT1 and GLUT9 proteins in kidney,and increase the expression levels of OAT1 and OAT3 proteins.Conclusion:Zangdangshen[Codonopsis thalictrifolia Wall.var.mollis(Chipp.)L.T.Shen]extract has a protective effect on hyperuricemia mice induced by yeast extract paste combined with potassium oxonate,and its mechanism may be through inhibiting XOD activity and regulating uric acid transporter.