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作 者:吴林秀[1] 梁红[1] 赵应学[2] 何华梅 梁杏梅[1] 周维海 甄汉深[4] 黄敏琪[1] 刘喜华[1] WU Lin-xiu;LIANG Hong;ZHAO Ying-xue;HE Hua-mei;LIANG Xing-mei;ZHOU Wei-hai;ZHEN Han-shen;HUANG Min-qi;LIU Xi-hua(Guangxi Medical College,Nanning 530023,China;Guangxi Jiangbin Hospital,Nanning 530021,China;Guangxi Kekang Technology Group Co.,Ltd.,Nanning 530001,China;Guangxi University of Traditional Chinese Medicine,Nanning 530001,China)
机构地区:[1]广西卫生职业技术学院,广西南宁530023 [2]广西壮族自治区江滨医院,广西南宁530021 [3]广西科康科技集团有限公司,广西南宁530001 [4]广西中医药大学,广西南宁530001
出 处:《中草药》2020年第22期5776-5780,共5页Chinese Traditional and Herbal Drugs
基 金:广西自然科学基金资助项目(2018GXNSFAA281093);广西教育厅科研项目(2020KY43012);广西科学研究与技术开发重大专项计划项目(桂科重1355001-5-9)。
摘 要: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(30mg/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;q RT-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。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.
关 键 词:水蛭素 高尿酸血症 有机阴离子转运蛋白1 尿酸盐转运体1 葡萄糖转运体9
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