罗格列酮对尿酸代谢的影响及机制探讨  

Impact of rosiglitazone on uric acid metabolism and its mechanism

作　　者：苗志敏[1] 王灿[1] 孟冬梅[1] 王静[1] 周玉娇[1] 李长贵[1] 

机构地区：[1]青岛大学医学院附属医院,山东省代谢性疾病重点实验室,266003

出　　处：《中华内分泌代谢杂志》2010年第9期792-796,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金资助项目（30470821,30570890）

摘　　要：目的 观察高水平胰岛素是否导致血尿酸浓度的升高,胰岛素增敏剂罗格列酮能否改善高尿酸血症,并进行机制探讨.方法 将自发2型糖尿病伴代谢综合征的OLETF大鼠及其同系的正常对照LETO大鼠各60只随机分为对照组、实验组和干预组,分别给予正常饮食、高嘌呤饮食加腺嘌呤灌胃及罗格列酮干预3周,测量各组大鼠体重、血尿酸、胰岛素、甘油三酯、总胆固醇等指标,检测肾皮质尿酸转运子（UAT）和尿酸盐转运子1（URAT1）mRNA表达.以不同浓度胰岛素孵育HK-2细胞24 h,检测其UAT mRNA表达.结果 （1）在正常饮食状态下,OLETF大鼠血胰岛素水平明显高于LETO大鼠（P〈0.05）,尿酸水平差异无统计学意义.（2）高嘌呤饮食喂养和腺嘌呤灌胃3周后,OLETF大鼠血胰岛素水平明显高于LETO大鼠[（61.83±12.13对36.73±12.73）μIU/ml,P〈0.05],高尿酸血症的发病率（76.92%对36.13%,P〈0.01）和血尿酸[（327.75±45.73对264.40±36.32）μmol/L,P〈0.01]水平明显高于LETO大鼠.（3）与实验组OLETF大鼠相比,罗格列酮干预3周后胰岛素水平明显下降[（41.3±10.2对61.8±12.1）μIU/ml,P〈0.05],血尿酸水平明显降低[（198.0±45.4对236.9±29.30）μmol/L,P〈0.05],尿尿酸排泄量明显增加[（5 644±371对4 692±278）μmol/L,P〈0.05].（4）实验组OLETF大鼠血胰岛素水平与对照组OLETF大鼠无明显差异,肾皮质URAT1和UAT mRNA表达差异亦无统计学意义,而罗格列酮干预后URAT1 mRNA表达明显降低,UAT mRNA表达明显增加.（5）随着培养液中胰岛素浓度的增加,HK-2细胞UATmRNA表达量逐渐减少.结论 胰岛素增敏剂罗格列酮可通过调节UAT和URAT1 mRNA的表达,降低高胰岛素血症诱发的高尿酸血症.Objective To observe whether high-level insulin increases serum uric acid level and rosiglitazone improves hyperuricemia, and to explore the mechanism. Methods OLETF rats with spontaneous type 2 diabetes complicated with metabolic syndrome and normal control LETO rats were randomly divided into three groups （n=20 each）. The animals were fed with standard chow diet in control group, high-purine diet and adenine administered intragastrically in experimental group, and rosiglitazone in interventional group. Body weight, serum levels of uric acid, insulin, triglyceride （ TG ） , and total cholesterol （ TC ） were measured after 3 weeks. Urate transporter 1 （ URAT1 ） and uric acid transporter （UAT） mRNA expressions in renal cortex were examined. HK-2 cells were incubated with various concentrations of insulin for 24 hours. UAT mRNA expression in HK-2 cells was examined. Results （ 1 ） In control group, the insulin level of OLETF rats was significantly higher than that of LETO rats （ P〈0. 05 ）, and there was no significant difference in serum uric acid level between OLETF and LETO rats. （2）In experimental groups, the insulin level in OLETF rats was significantly higher than that in LETO rats [（61.83±12.13 vs 36.73±12.73 ）μIU/ml ,P〈0. 05], and the incidence of hyperuricemia （76.92% vs 36.13%,P〈0.01 ） and serum uric acid level[（ 327.75 ±45.73 vs 264.40±36.32 ） μmol/L, P〈0. 01]in OLETF rats were significantly higher than those in LETO rats. （3） Insulin[（41.3± 10.2 vs 61.8±12. 1 ）μIU/ml,P〈0. 05]and uric acid[（ 198.0±45.4 vs 236.9±29.30 ） μmol/L, P〈0. 05]levels in OLETF rats in interventional group were significantly lower than those of OLETF rats in experimental group, meanwhile the amount of urinary uric acid excretion was significantly increased[（5 644±371 vs 4 692±278 ） μ mol/L, P〈0. 05]. （4） There was no significant difference in insulin level and the expressions of URAT1 and UAT mRNA in renal cortex between OLETF rats in control

关 键 词：罗格列酮 胰岛素 高尿酸血症 尿酸盐转运子1 尿酸盐转运子 

分 类 号：R96[医药卫生—药理学]