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目的:研究高尿酸条件下尿酸盐阴离子转运体1(Urate anion exchanger 1,URAT1)、葡萄糖转运体9(glucose transporter 9,GLUT9)、有机阴离子转运体10(Organic Anion Transporter 10,OAT10)基因表达的动态变化。方法:(1)研究不同剂量尿酸对小鼠血尿酸水平的影响:遵循随机化原则将50只雄性昆明种小鼠分为5组(每组10只):分别为正常组、尿酸每天100、200、300、400mg/kg剂量组。每天2次腹腔注射尿酸磷酸盐溶液,共造模14天,确定最佳剂量。(2)确定最佳剂量后,小鼠腹腔注射最佳剂量尿酸每天300 mg/kg,复制高尿酸血症模型。在给予尿酸1、3、7、14天处死小鼠,用磷钨酸法测定小鼠血清尿酸水平和肝尿酸含量,用RT-PCR检测小鼠肾脏尿酸盐重吸收转运体URAT1、GLUT9、OAT10基因表达水平。结果:(1)腹腔注射尿酸每天300 mg/kg及400mg/kg能有效升高小鼠血尿酸水平(P<0.01),但400 mg/kg组小鼠死亡率高。而尿酸100、200 mg/kg组与正常组相比无统计学差异,300 mg/kg为最佳剂量;(2)与正常组相比,模型组血尿酸水平在造模1、3、7、14天均升高(P<0.05),造模成功;与正常组相比,模型组肝匀浆尿酸含量在造模1天显著升高(P<0.01);而造模3天、7天及14天均无统计学差异;与正常对照组相比,模型组小鼠肾脏GLUT9基因表达水平在1、3、14天均增加(P<0.05);与正常对照组相比,模型组小鼠肾脏URAT1和OAT10基因表达水平在各时间点均无显著变化(P>0.05)。结论:在尿酸诱导的高尿酸血症小鼠模型上,模型组GLUT9基因在给予尿酸1、3、14天后表达均上调,但URAT1、OAT10的基因表达均无显著变化。
Objective: To investigate the expression of Urate anion exchanger 1 (URAT1), glucose transporter 9 (GLUT9) and organic anion transporter 10 (OAT10) gene under hyperuricemic conditions Dynamic changes. Methods: (1) To study the effects of different doses of uric acid on blood uric acid levels in mice: According to the principle of randomization, 50 male Kunming mice were divided into 5 groups (10 in each group): normal group, uric acid 100, 200,300,400 mg / kg dose group. 2 times a day intraperitoneal injection of uric acid phosphate solution, a total of 14 days modeling to determine the optimal dose. (2) After determining the optimal dose, the mice were injected intraperitoneally with the optimal dose of uric acid 300 mg / kg per day to replicate the hyperuricemia model. Mice were sacrificed at 1, 3, 7 and 14 days after uric acid administration, serum uric acid levels and hepatic uric acid levels were determined by phosphotungstic acid method. URAT1, GLUT9, OAT10 gene expression levels. Results: (1) Uric acid intraperitoneal injection of 300 mg / kg and 400 mg / kg daily increased serum uric acid level (P <0.01), but the mortality of 400 mg / kg group mice was high. While uric acid 100,200 mg / kg group compared with the normal group was no significant difference, 300 mg / kg for the best dose; (2) Compared with the normal group, the model group serum uric acid levels in the modeling 1,3,7 (P <0.05). The uric acid content of liver homogenate in model group was significantly higher than that in normal group at 1 day (P <0.01) (P <0.05). Compared with the normal control group, the expression of GLUT9 gene in kidney of model group increased on the 1st, 3rd, 14th day (P <0.05). Compared with the normal control group, the model group The expression of URAT1 and OAT10 mRNA in mouse kidney had no significant changes at all time points (P> 0.05). CONCLUSION: In uric acid-induced hyperuricemia mouse model, the expression of GLUT9 in model group was up-regulated on the 1st, 14th and 14th days after administration of uric acid, but there was no significant change in the gene expression of URAT1 and OAT10.