茯苓水提物对高尿酸血症大鼠rURAT1 rOAT1和rOCT2表达的影响
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摘要
目的考察茯苓水提物对高尿酸血症大鼠肾脏组织中尿酸转运体1(rURAT1)、有机阴离子转运体1(rOAT1)和有机阳离子转运体2(rOCT2)表达的影响,探讨茯苓降低血尿酸水平的机制。方法将右侧肾脏摘除的48只大鼠随机分为6组:手术对照组、模型组、别嘌呤醇阳性对照组,茯苓水提物高、中、低剂量组。药物干预28d,实验期间定期检测血尿酸和血清肌酐水平,采用免疫印迹法检测各组大鼠肾脏组织中rURAT1、rOAT1和rOCT2的表达。结果茯苓水提物高、中、低剂量组的血尿酸水平均较模型组大鼠明显降低;肾脏组织中rOAT1和rOCT2的表达均较模型组大鼠明显升高,而其rURAT较模型组大鼠显著下降,差异均有统计学意义(P<0.05)。结论茯苓水提物通过调节肾脏组织中rURAT1、rOAT1和rOCT2的表达,从而发挥促进高尿酸血症大鼠尿酸的排泄作用。
Objective To observe the efficacy of Poria cocos on the expression of urate transporter 1(rURAT1),organic anion transporter 1(rOAT1)and organic cation transporter 2(rOCT2)in hyperuricemia rats.Methods 48 rats were randomly divided into 6groups after a right nephrectomy including operation control group,model group,allopurinol group,high dosage Poria cocos group,middle dosage Poria cocos group,low dosage Poria cocos group.Levels of serum uric acid(SUA)and creatinine(CR)were measured every fortnightly.Protein levels of rURAT1,rOAT1 and rOCT2in the kidney were analyzed by western blotting.Results The administration of Poria cocos significantly reduced SUA concentration.After administration Poria cocos,the expression of rOAT1 and rOCT2were increased,while the expression of rURAT1 was significantly reduced compared to that of the operation model rats.Conclusion Poria cocos could increase urine excretion of SUA and improve the renal function via regulation of rURAT1,rOAT1 and rOCT2in the kidney.
Objective To observe the efficacy of Poria cocos on the expression of urate transporter 1(rURAT1),organic anion transporter 1(rOAT1)and organic cation transporter 2(rOCT2)in hyperuricemia rats.Methods 48 rats were randomly divided into 6groups after a right nephrectomy including operation control group,model group,allopurinol group,high dosage Poria cocos group,middle dosage Poria cocos group,low dosage Poria cocos group.Levels of serum uric acid(SUA)and creatinine(CR)were measured every fortnightly.Protein levels of rURAT1,rOAT1 and rOCT2in the kidney were analyzed by western blotting.Results The administration of Poria cocos significantly reduced SUA concentration.After administration Poria cocos,the expression of rOAT1 and rOCT2were increased,while the expression of rURAT1 was significantly reduced compared to that of the operation model rats.Conclusion Poria cocos could increase urine excretion of SUA and improve the renal function via regulation of rURAT1,rOAT1 and rOCT2in the kidney.
引文
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[10]苏筠霞,李建华,刘天喜,等.萆薢对尿酸性肾病大鼠TNF-α、MCP-1和ICAM-1表达的影响[J].中成药,2013,35(5):1088-1091.
[11]Chen L,Yin H,Lan Z,et al.Anti-hyperuricemic and nephroprotective effects of Smilax china L[J].Journal of ethnopharmacology,2011,135(2):399-405.
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[13]Bobulescu IA,Moe OW.Renal transport of uric acid:evolving concepts and uncertainties[J].Advances in chronic kidney disease,2012,19(6):358-371.
[14]Lipkowitz MS.Regulation of uric acid excretion by the kidney[J].Curr Rheumatol Rep,2012,14(2):179-388.
[15]Riches PL,Wright AF,Ralston SH.Recent insights into the pathogenesis of hyperuricaemia and gout[J].Human molecular genetics,2009,18(R2):R177-R184.
[16]陈伟,唐德燊.人肾脏尿酸转运机制及影响因素的研究进展[J].广东医学院学报,2009,27(6):678-681.
[17]Kim S,Lee CH,Kang CM,et al.Effects of Increased Uric Acid Intake on the Abundance of Urate-anion exchanger and Organic Anion Transporter Proteins in the Rat Kidney[J].Electrolyte&blood pressure:E&BP,2007,5(2):62-67.
[18]Sato M,Wakayama T,Mamada H,et al.Identification and functional characterization of uric acid transporter Urat1(Slc22a12)in rats[J].Biochimica et biophysica acta,2011,1808(6):1441-1447.
[19]Reznichenko A,Sinkeler SJ,Snieder H,et al.SLC22A2is associated with tubular creatinine secretion and bias of estimated GFR in renal transplantation[J].Physiol Genomics,2013,45(6):201-209.
[2]Hediger MA,Johnson RJ,Miyazaki H,et al.Molecular physiology of urate transport[J].Physiology(Bethesda),2005,20(2):125-133.
[3]So A,Thorens B.Uric acid transport and disease[J].The Journal of clinical investigation,2010,120(6):1791-1799.
[4]Hu QH,Jiao RQ,Wang X,et al.Simiao pill ameliorates urate underexcretion and renal dysfunction in hyperuricemic mice[J].Journal of ethnopharmacology,2010,128(3):685-692.
[5]Torres RJ,De Miguel E,Bailen R,et al.Absence of SLC22A12/URAT1gene mutations in patients with primary gout[J].J Rheumatol,2012,39(9):1901.
[6]Vazquez-Mellado J,Jimenez-Vaca AL,Cuevas-Covarrubias S,et al.Molecular analysis of the SLC22A12(URAT1)gene in patients with primary gout[J].Rheumatology(Oxford),2007,46(2):215-219.
[7]郭淑云,张薇,张琰,等.土茯苓对高尿酸症小鼠作用的研究[J].海南医学院学报,2012,18(2):165-167.
[8]Su JX,Wei YH,Liu ML,et al.Anti-hyperuricemic and nephroprotective effects of Rhizoma Dioscoreae septemlobae extracts and its main component dioscin via regulation of mOAT1,mURAT1and mOCT2in hypertensive mice[J].Arch Pharm Res,2014,37(10):1336-1344.
[9]Iwaki K,Yonetani Y.Hyperuricemic effects of cholinergic agents in rats[J].Japanese journal of pharmacology,1982,32(2):343-349.
[10]苏筠霞,李建华,刘天喜,等.萆薢对尿酸性肾病大鼠TNF-α、MCP-1和ICAM-1表达的影响[J].中成药,2013,35(5):1088-1091.
[11]Chen L,Yin H,Lan Z,et al.Anti-hyperuricemic and nephroprotective effects of Smilax china L[J].Journal of ethnopharmacology,2011,135(2):399-405.
[12]Richette P,Doherty M,Pascual E,et al.2016updated EULAR evidence-based recommendations for the management of gout[J].Annals of the rheumatic diseases,2016,DOI:10.1136/annrheumdis-2016-209707.
[13]Bobulescu IA,Moe OW.Renal transport of uric acid:evolving concepts and uncertainties[J].Advances in chronic kidney disease,2012,19(6):358-371.
[14]Lipkowitz MS.Regulation of uric acid excretion by the kidney[J].Curr Rheumatol Rep,2012,14(2):179-388.
[15]Riches PL,Wright AF,Ralston SH.Recent insights into the pathogenesis of hyperuricaemia and gout[J].Human molecular genetics,2009,18(R2):R177-R184.
[16]陈伟,唐德燊.人肾脏尿酸转运机制及影响因素的研究进展[J].广东医学院学报,2009,27(6):678-681.
[17]Kim S,Lee CH,Kang CM,et al.Effects of Increased Uric Acid Intake on the Abundance of Urate-anion exchanger and Organic Anion Transporter Proteins in the Rat Kidney[J].Electrolyte&blood pressure:E&BP,2007,5(2):62-67.
[18]Sato M,Wakayama T,Mamada H,et al.Identification and functional characterization of uric acid transporter Urat1(Slc22a12)in rats[J].Biochimica et biophysica acta,2011,1808(6):1441-1447.
[19]Reznichenko A,Sinkeler SJ,Snieder H,et al.SLC22A2is associated with tubular creatinine secretion and bias of estimated GFR in renal transplantation[J].Physiol Genomics,2013,45(6):201-209.