叶下珠提取物对高尿酸血症小鼠模型尿酸水平的影响

Study on effects of Phyllanthusurinaria L extract Intervene Uric Acid in hyperuricemia mice

目的:考察叶下珠(Phyllanthusurinaria L)提取物在高尿酸血症小鼠中降尿酸的效果。方法:随机将60只小鼠以体质量平均分为6组,分别是阴性对照组、模型组、别嘌呤醇组(40 mg/kg)和叶下珠提取物低、中、高剂量组(15、30、45 mg/kg),各组小鼠连续7 d给予小鼠腹腔注射氧嗪酸钾盐300 mg/kg来抑制小鼠尿酸酶活性建立高尿酸血症模型,阴性对照组给予等体积的生理盐水。注射氧嗪酸钾盐1 h后各组灌胃相应药物,连续灌胃8 d后,取血检测血清的尿酸(uric acid,UA)、肌酐(creatinine,Cre)、血尿素氮(blood urea ni-trogen,BUN)含量,取肝脏并测定其黄嘌呤氧化酶(xanthine oxidase,XOD)的活性水平;各组小鼠肾脏组织经HE染色后,光镜下观察其病理改变。各组小鼠肾脏尿酸转运体(uric acid transporter 1,URAT1)蛋白的表达水平用Western blot法检测。结果:各组高尿酸血症小鼠模型中,叶下珠提取物(15、30、45 mg/kg)剂量组能明显降低UA、BUN和Cre水平和肝脏XOD活性(P<0.01),叶下珠提取物高剂量组表现尤为突出,接近别嘌呤醇组;且能改善高尿酸血症小鼠肾脏病理学变化,优于别嘌呤醇;机制研究表明,模型组的URAT1蛋白表达明显高于空白对照组(P<0.05),叶下珠提取物高剂量组URAT1蛋白表达明显低于模型组(P<0.05),且与别嘌呤醇持平。结论:叶下珠提取物能有效降低高尿酸血症模型小鼠的尿酸水平,可能通过降低肝脏XOD活性和抑制URAT1蛋白表达及减少肾脏病变发挥作用。

Objective:To investigate the effect of Phyllanthusurinaria L extract on hyperuricemia mice.Methods:Totally 60 mice were randomly divided into 6 groups according to their body weight,namely the negative control group,model group,allopurinol group(40 mg/kg)and low,medium and high dose groups of Phyllanthusurinaria extract(15,30,45 mg/kg).Mice in each group were given intraperitoneal injection of 300 mg/kg of oxazinonate potassium salt for 7 consecutive days to inhibit the activity of uricase in mice to establish a hyperuricemia model.The negative control group was given an equal volume of normal saline.One hour after the injection of oxazinate potassium salt,the corresponding drugs were administered in each group.After continuous intragastric administration for 8 days,blood was taken to test serum uric acid(UA),creatinine(Cre),and blood urea nitrogen(blood urea).ni-trogen(BUN)content,the livers were taken and the xanthine oxidase(xanthine oxidase,XOD)activity levels were determined;the kidney tissues of each group of mice were stained with HE,and the pathological changes were observed under light microscope.The expression levels of uric acid transporter(URAT1)protein in the kidneys of mice in each group were detected by Western blot.Results:In each group of hyperuricemia mice models,Phyllanthus urinaria extract(15,30,45 mg/kg)dose group can significantly reduce UA,BUN and Cre levels and liver XOD activity(P<0.01).The performance of the high-dose extract group of Phyllanthus urinaria was particularly outstanding,close to the allopurinol group;and can improve the pathological changes of the kidney in hyperuricemia mice,better than allopurinol;mechanism studies showed that the URAT1 protein expression in the model group was significantly higher than that of the blank control Group(P<0.05),the expression of URAT1 protein in Phyllanthus urinaria high-dose group was significantly lower than that of model group(P<0.05),and remained at the same level of allopurinol.Conclusion:Phyllanthus urinaria extract can effectively reduce the level of uric acid in hyperuricemia model mice,possibly by reducing liver XOD activity,inhibiting URAT1 protein expression and reducing kidney disease.