芹菜素对氧嗪酸钾盐致高尿酸血症小鼠的降尿酸及肾保护作用机制研究

Mechanism Study on Effects of Apigenin on Reducing Uric Acid and Renal Protection in Oteracil Potassium-induced Hyperuricemia Mice

目的:研究芹菜素对氧嗪酸钾盐致高尿酸血症小鼠的降尿酸及肾保护作用机制。方法:将50只小鼠按体质量随机分为正常组、模型组、别嘌呤醇组(5 mg/kg)与芹菜素低、高剂量组(40、80 mg/kg),每组10只。除正常组外,其余各组小鼠ig氧嗪酸钾250 mg/kg复制高尿酸血症模型,造模后1 h,各给药组小鼠ig相应药物,正常组和模型组小鼠ig等体积生理盐水,每天1次,连续7d。测定各组小鼠血尿酸、尿尿酸、24 h尿肌酐水平和肾脏转运体相关蛋白(m URAT1、m OCT1、m OCT2、m OCTN1、m OCTN2)表达水平。结果:与正常组比较,模型组小鼠血尿酸、尿尿酸、m URAT1水平显著升高,m OCT1、m OCT2、m OCTN1、m OCTN2水平和24h尿肌酐水平显著降低(P<0.01或P<0.001);与模型组比较,芹菜素低、高剂量组及别嘌呤醇组小鼠血尿酸、尿尿酸、m URAT1水平显著降低,24 h尿肌酐水平、m OCT1、m OCT2、m OCTN1和m OCTN2水平显著升高(P<0.05或P<0.01或P<0.001)。结论:芹菜素能降低氧嗪酸钾盐致高尿酸血症小鼠的尿酸水平,保护肾脏;其作用机制可能与下调小鼠肾脏中m URAT1水平,上调m OCTN1、m OCTN2、m OCT1及m OCT2水平相关。

OBJECTIVE：To investigate the mechanism of the effects of apigenin on reducing uric acid and renal protection in oteracil potassium-induced hyperuricemia mice.METHODS：50 mice were randomly divided into normal group,model group,allopurinol group（5 mg/kg）,apigenin low-dose and high-dose groups（40,80 mg/kg）,with 10 mice in each group.Except for normal group,other groups were given oteracil potassium 250 mg/kg intragastrically to induce hyperuricemia model;1 h after modeling,treatment groups were given relevant medicine intragastrically,and normal group and model group were given constant volume of normal saline intragastrically,once a day,for consecutive 7 d.Blood uric acid,urine uric acid and 24 h creatinine levels,the expression of kidney transporter associated protein（m URAT1,m OCT1,m OCT2,m OCTN1 and m OCTN2） were all determined in each group.RESULTS：Compared with normal group,blood uric acid,urine uric acid and m URAT1 levels of model group were significantly increased,while the expressions of m OCT1,m OCT2,m OCTN1 and m OCTN2,24 h creatinine were significantly decreased（P〈0.01 or P〈0.001）.Compared with model group,blood uric acid,urine uric acid and m URAT1 levels of apigenin low-dose and high-dose groups,allopurinol group were significantly decreased,while 24 h creatinine,the expressions of m OCT1,m OCT2,m OCTN1 and m OCTN2 were increased significantly（P〈0.05 or P〈0.01 or P〈0.001）.CONCLUSIONS：Apigenin can reduce uric acid level of oteracil potassium-induced hyperuricemia mice and propect kidney,the mechanism of which may be associated with down-regulating the expression of m URAT1 and up-regulating the expressions of m OCTN1,m OCTN2,m OCT1 and m OCT2.