泄浊除痹方对高尿酸血症小鼠尿酸及URAT1的影响

目的:观察泄浊除痹方对高尿酸血症小鼠尿酸及人尿酸盐阴离子交换器1(URAT1)的影响,探讨该方的作用机制.方法:60只SPF级昆明种雄性小鼠随机分成泄浊除痹方高、中、低剂量组、苯溴马隆组、造模组、空白对照组,应用酵母法联合尿酸酶抑制法制备高尿酸血症模型,造模开始后第7天,药物治疗组分别给予泄浊除痹方颗粒(37.5,18.75,9.375 g·kg -·d-1)、苯溴马隆片(20 mg·kg-1 ·d-1)每日1次ig,共15 d,测定血尿酸并应用荧光定量PCR法测定URAT1基因表达量.结果:泄浊除痹方高、中、低剂量组均可降低小鼠血尿酸,分别为(209.00±24.54),(234.50 ±31.38),(273.88±25.04) μmol·L-1,与模型组比(P＜0.05),呈剂量依赖关系;高、中剂量组疗效与苯溴马隆(208.70±33.70) μmol· L-1相当;泄浊除痹方对URAT1有一定抑制作用(P＜0.05).结论:泄浊除痹方可有效降低模型小鼠血尿酸,可能通过下调URAT1基因的表达,抑制尿酸盐重吸收过程而达到促进尿酸排泄作用.

Study on Influence of Xiezhuo Chubi Decoction on Uric Acid and URAT1 in Hyperuricemia Mice

Objective:To investigate the influence of Xiezhuo Chubi decoction on uric acid and urate transporter 1(URAT1) gene in hyperuricemia mice,that to search for the mechanism of reducing uric acid.Method: Sixty Kunming male mice of SPF grade were randomly divided into high-,medium-,low-dose Xiezhuo Chubi decoction group,Benzbromarone group,model group and control group.All mice were established with yeast method combined with uricase inhibition method to build hyperuricemia model except control group.The corresponding drugs were administrated at the 7th day(Xiezhuo Chubi decoction 37.5,18.75,9.375 g·kg-1·d-1,benzbromarone 20 mg·kg-1·d-1,ig,once per day for 15 days).The blood was obtained to detect uric acid levels.Simultaneously,the kidneys were removed to detect mRNA expressions of URAT1 with fluorescence quantitative PCR.Result: Imposed by different factors to each group,oral administration of Xiezhuo Chubi decoction could significantly reduce the uric acid in mice in a dose-dependent manner(209.00±24.54),(234.50±31.38),(273.88±25.04)μmol·L-1(P<0.05).The effects of high-and medium-dose Xiezhuo Chubi decoction group were similar with benzbromarone group(208.70±33.70) μmol·L-1.The mRNA expressions of URAT1 were decreased significantly in Xiezhuo Chubi decoction group than that in model group(P<0.05).Conclusion: Xiezhuo Chubi decoction could reduce the uric acid effectively.Its mechanism might be the action of inhibition to the mRNA expressions of URAT1 in kidney.