水蛭素对高尿酸血症大鼠尿酸盐转运体OAT1、URAT1、GLUT9表达的影响

目的 探究水蛭素对高尿酸血症大鼠的作用及机制。方法 雄性Wistar大鼠随机分为对照组、模型组、别嘌醇（30 mg/kg）组和水蛭素低、中、高剂量（0.2、0.4、0.8 g/kg）组。大鼠ig氧嗪酸钾（0.75 g/kg），1次/d，连续5周，建立高尿酸血症模型；同时各给药组分别ig相应剂量的药物，1次/d，连续5周。采用生化法检测大鼠血清和尿液中的尿酸水平；免疫组化法测定肾组织中有机阴离子转运蛋白1（organic anion transporter 1，OAT1）水平；Western blotting法测定肾组织中葡萄糖转运体9（glucose transporter 9，GLUT9）、OAT1、尿酸盐转运体1（urate transporter 1，URAT1）蛋白表达；qRT-PCR检测肾组织中GLUT9、OAT1、URAT1 mRNA表达。结果 模型组大鼠血清和尿液中尿酸水平显著升高（P<0.01），GLUT9、URAT1 mRNA和蛋白表达水平明显升高（P<0.01），OAT1 mRNA和蛋白表达水平明显降低（P<0.01）；与模型组比较，水蛭素可显著降低大鼠血清和尿液中尿酸水平（P<0.01），显著下调GLUT9、URAT1 mRNA和蛋白表达水平（P<0.01），显著上调OAT1 mRNA和蛋白表达水平（P<0.01）。结论 水蛭素可通过调控高尿酸血症大鼠肾脏尿酸盐转运体OAT1、URAT1、GLUT9的表达，从而发挥降尿酸作用。

Effect of hirudin on expressions of urate transporters OAT1, URAT1 and GLUT9 in hyperuricemia rats

Objective To explore the effect of hirudin on hyperuricemia rats and its mechanism. Methods Male Wistar rats were randomly divided into control group, model group, allopurinol (30 mg/kg) group, hirudin low-, middle- and high-dose (0.2, 0.4, 0.8 g/kg) group. Rats were ig potassium oxonate (0.75 g/kg) to induce hyperglycemia model, once a day for five weeks. And all administration groups were respectively ig corresponding doses of drugs. The level of uric acid in serum and urine of rats were measured by biochemical method; The level of organic anion transporter 1 (OAT1) in kidney was measured by immunohistochemistry; The protein expressions of glucose transporter 9 (GLUT9), OAT1 and urate transporter 1 (URAT1) in kidney were measured by western blotting; The expression levels of GLUT9, OAT1 and URAT1 mRNA in kidney were detected by qRT-PCR. Results Compared with control group, the level of uric acid in serum and urine of rats in model group was significantly increased (P<0.01), the expressions of GLUT9, URAT1 mRNA and protein were significantly increased (P<0.01), the expressions of OAT1 mRNA and protein were significantly decreased (P<0.01). Compared with model group, the level of uric acid in serum and urine of rats in hirudin group were significantly decreased (P<0.01), the expressions of GLUT9, URAT1 mRNA and protein were significantly reduced (P<0.01), the expressions of OAT1 mRNA and protein were significantly increased (P<0.01). Conclusion Hirudin can reduce the uric acid by regulating the expressions of renal urate transporters OAT1, URAT1 and GLUT9 in hyperuricemia rats.