G lut9在果糖诱导大鼠高尿酸血症中的作用

摘要

[ ABSTRACT] AIM:To explore the effect of renal transporter glucose transporter 9 ( Glu9 ) on hyperuricemia in the rats induced by fructose.METHODS:SD male rats (n=30) were randomly divided into normal group, model group and benzbromarone group , according to the weight .The rats in normal group was given water , while the rats in model group and benzbromarone group were given 10%fructose solution to establish hyperuricemia model .At the same time , the rats in normal group and model group were given a gavage of distilled water , while the rats in benzbromarone group were given benzbromarone at the dose of 20 mg/kg.The rats were sacrificed on the 40th day.The serum uric acid (SUA) and urinary uric acid (UUA) were detected to calculate the clearance rate of uric acid (CUA) in the kidney.The activity of hepatic xanthine oxidase ( XOD) was also measured .The expression of renal Glut 9 at mRNA and protein levels was determined by RT-qPCR and immunohistochemical staining .RESULTS:From the 20th day to the 40th day, the SUA in model group was significantly higher than that in normal group , but the UUA and CUA had no difference .On the 20th day, the SUA in benzbromarone group was markedly decreased as compared with model group , but UUA and CUA had no significant differ-ence.On the 40th day, the hepatic XOD activity in model group was significantly elevated , and no difference of XOD be-tween model group and the benzbromarone group was observed .Compared with normal group , the protein expression of Glut9 in the renal tissues of model group were markedly increased , and that in benzbromarone group was significantly lower than that in model group .However, no difference of the Glut9 mRNA expression was observed among groups .CONCLU-SION:Fructose drinking induces hyperuricemia in rats , which is probably related to the up-regulation of renal Glut9 ex-pression at protein level , and the increase in the reabsorption of uric acid in the kidneys .%目的：观察肾脏转运蛋白葡萄糖转运体9（Glut9）与肾脏尿酸排泄的关系，探讨果糖诱导的高尿酸血症的病理机制。方法：将30只雄性SD大鼠按体质量随机分为正常组、模型组与苯溴马隆组，正常组给予清水，模型组与苯溴马隆组给予10％果糖饮水建立高尿酸血症模型。正常组与模型组给予清水灌胃，苯溴马隆组给予20 mg／kg苯溴马隆灌胃，实验第42天处死。检测大鼠血清尿酸和尿尿酸水平，计算肾脏尿酸清除率，并测定肝脏黄嘌呤氧化酶活性。利用免疫组化观察Glut9在各组大鼠肾脏的表达位点及其蛋白表达含量，实时荧光定量PCR （ RT-qPCR）检测各组大鼠肾脏Glut9的mRNA表达水平。结果：实验第20～40天，与正常组比较，模型组的血尿酸水平显著升高，尿尿酸与尿酸清除率的差异无统计学显著性；实验第20天，与模型组比较，苯溴马隆组的血尿酸水平显著降低，但尿尿酸和尿酸清除率的差异无统计学显著性。实验第40天，模型组的肝脏黄嘌呤酶活性较正常组显著升高，但与模型组比较差异无统计学显著性。免疫组化实验结果显示，与正常组比较，模型组肾脏的Glut9蛋白表达显著增加；苯溴马隆组肾脏的Glut9蛋白表达少于模型组。 RT-qPCR结果显示，各组肾脏Glut9 mRNA表达水平之间的差异并无统计学显著性。结论：10％果糖饮水可成功诱导大鼠高尿酸血症模型；果糖诱导高尿酸血症病理机制可能与上调肾脏Glut9蛋白水平、增加肾脏对尿酸的重吸收有关。