高脂血症阶段自发代谢综合征及2型糖尿病模型大鼠肾小管上皮细胞电压敏感性尿酸盐转运体的表达

Expression of voltage sensitive urate transporter in renal epithelial cells of Otsuka Long 2 Evans Tokushima Fatty rats at hyperlipemia stage

目的:观察自发代谢综合征及2型糖尿病动物模型(OLETF大鼠)在高脂血症阶段肾小管上皮细胞电压敏感性尿酸盐转运体的表达。方法:实验于2006-05/10在青岛大学医学院附属医院医学动物实验中心和分子中心实验室完成。选择雄性4周龄OLETF大鼠10只为OLETF组,同系4周龄LETO大鼠(非糖尿病)10只为对照,基础饮食至11周龄。采用定量RT-PCR方法检测电压敏感性尿酸盐转运体在肾皮质中的表达,记录并比较两组大鼠7周龄和11周龄时体质量、体长,及11周龄三酰甘油、总胆固醇、尿酸、肌酐、尿素氮和高密度脂蛋白。结果:20只大鼠均进入结果分析。①7及11周龄时OLETF大鼠体质量大于同龄LETO大鼠[7周龄:(282.42±18.75),(224.58±17.33)g;11周龄:(380.33±30.98),(301.58±25.15)g;P均<0.05],体长也大于同龄LETO大鼠[7周龄:(18.80±0.79),(17.00±0.82)cm,P<0.05;11周龄:(20.08±0.67),(18.17±1.19)cm,P<0.01];但Lee's指数无明显差别。②11周龄时,OLETF大鼠三酰甘油和总胆固醇高于LETO大鼠[(1.24±0.43),(0.41±0.14)mmol/L;(1.92±0.19),(1.46±0.15);P均<0.05];尿酸较LETO组增高,但差异不显著,其他指标两组无明显差别。③OLETF大鼠大鼠电压敏感性尿酸盐转运体mRNA的表达水平低于LETO大鼠(0.32±0.12,1.12±0.63,P<0.05)。结论:OLETF大鼠在高脂血症阶段,随着尿酸的升高,电压敏感性尿酸盐转运体mRNA的表达明显降低,可能通过下调电压敏感性尿酸盐转运体的表达,来调节体内尿酸的排泄,脂代谢紊乱和高尿酸血症可能通过该纽带相联系。

AIM： To detect the expressions of voltage sensitive urate transporter （UAT） in the renal epithelial cells of Otsuka Long 2 Evans Tokushima Fatty （OLETF） rats in the stage of hyperlipemia. METHODS： The experiment was finished in Medical Animal Experimental Center and Molecular Biology Laboratory of the Affiliated Hospital of Qiogdao University Medical College from May to October in 2006. Ten four-week male OLETF rats were experimental group, while another ten four-week male LETO rats were included in normal control group. They were all fed till the 11^th week. The expression levels of UAT in renal cortex were detected by quantitative reverse transcript polymerase chain reaction. Weights and heights of rats ware recorded and compared in the seventh week and the eleventh week. Additionally triacylglycerol （TG）, total cholesterol （TC）, uric acid （UA）, creatinine （CRE）, urea nitrogen （UN） and high-density lipoprotein （HDL） ware detected in the eleventh week. RESULTS： All 20 rats were involved in the result analysis.①ln the seventh week and eleventh week, the weights and the heights of OLETF rats ware both higher than those of LETO rats [week 7： （282.42±18.75）, （224.58±17.33） g; week 11： （380.33±30.98）, （301.58±25.15） g; P〈 0.05; week 7： （18.80±0.79）, （17.00±0.82） cm, P〈 0.05; week 11： （20.08±0.67）, （18.17±1.19） cm, P 〈 0.01]. But Lee index had no significant difference between the two groups.②ln the experimental group, blood serum concentrations of TG and TC in rats at the age of 11 weeks ware significantly higher than that in the normal control group [（1.24±0.43）, （0.41±0.14） mmol/L; （1.92±0.19）, （1.46±0.15）; P 〈 0.05]. And UA content was increased compared with that of LETO rats. CRE, UN and HDL had no significant difference between the two groups.③UAT mRNA level in experimental group was obviously lower than that in the normal control group （0.32±0.12, 1.12±0.63, P 〈 0.05）. CONCLUSION： In the stage of hyperlipemia of OLETF rats, the expression of UAT mRNA is obviously reduced along with the increasing level of UA. OLETF rats may adjust the excretion of UA by the down-regulation of the UAT expression. The disorder of lipid metabolism may connect the hyperuricacidemia with the excretion.