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来氟米特对糖尿病大鼠肾组织单核趋化蛋白1、转化生长因子β_1表达的影响 被引量:8

Effect of leflunomide on renal expression of monocyte chemoattractant protein-1 and transforming growth factor-beta 1 in diabetic nephropathy rats
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摘要 目的探讨来氟米特对链脲佐菌素(streptozotocin,STZ)诱导的糖尿病大鼠肾组织单核趋化蛋白1(MCP-1)、转化生长因子β1(TGF-β1)表达的影响,进一步探索来氟米特对糖尿病大鼠肾脏的保护作用。方法健康雄性SD大鼠54只随机分为3组:正常对照组(NC组)、糖尿病组(DM组)、来氟米特干预组(DM+LEF组),每组18只。应用STZ诱导糖尿病模型,成模后,DM+LEF组给予来氟米特5mg.kg-1.d-1溶液灌胃,于实验第4、6、8周末,各组分别取6只大鼠留取24小时尿量测24小时尿蛋白定量,内眦静脉采血测血肌酐、尿素氮,光镜观察肾组织病理变化,采用链霉菌抗生物素蛋白-过氧化物酶连结法(streptavidin-perosidase,SP)观察肾组织中MCP-1、TGF-β1表达,采用反转录聚合酶链反应(RT-PCR)检测肾组织MCP-1、TGF-β1mRNA的表达。结果与DM组比较,DM+LEF组大鼠24小时尿蛋白定量明显减少(P<0.01),DM+LEF组比同期DM组病理改变明显减轻,经来氟米特干预后,DM+LEF组大鼠肾组织MCP-1、TGF-β1mRNA表达明显减少。结论来氟米特可能通过减少肾组织MCP-1、TGF-β1表达,减轻肾损害,起到保护糖尿病肾脏的作用。 Objective To explore the effects and renoprective mechanism of leflunomide on the kidney expression of monocyte chemoattractant protein-1(MCP-1),and transforming growth factor-beta 1(TGF-β1) in streptozotocin(STZ)-induced diabetic rats.Methods Fifty-four healthy male Sprague-Dawley rats were randomly divided into three groups:normal control group(NC group,n=18),diabetic group(DM group,n=18),leflunomide treatment group(DM+LEF group,n=18).Diabetic model was induced by STZ,the rats in DM+LEF group were given by intragastric administration with the solution of leflunomide 5 mg·kg-1·d-1.The six rats in batch were sacrificed in each group respectively at the weekend of 4th,6th and 8th,then,24 hour urinary volume,24 hour urinary protein,blood urea nitrogen(BUN),serum creatinine(SCr) and renal histopathological changes were measured and observed.The renal expressions of MCP-1,TGF-β1 were observed with streptavidin-perosidase(SP),and the renal expressions of MCP-1,TGF-β1mRNA were detected by RT-PCR.Results Compared with DM group,24 hour urinary protein in DM+LEF group significantly reduced(P0.01),the pathological changes in DM+LEF group significantly reduced.Renal expressions of MCP-1,TGF-β1mRNA decreased significantly.Conclusion Leflunomide can reduce the expressions of MCP-1,TGF-β1 in renal tissue,thus alleviating kidney damage,developing protective effects in diabetic nephropathy.
出处 《临床荟萃》 CAS 2012年第3期202-205,209,F0003,共6页 Clinical Focus
关键词 糖尿病肾病 炎症趋化因子类 转化生长因子-Β1 免疫组织化学 逆转录聚合酶链反应 来氟米特 diabetic nephropathies chemokines transforming growth factor beta1 immunohistochemistry reverse transcriptase polymerase chain reaction leflunomide
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参考文献12

  • 1林鹭平,李兴.链脲佐菌素诱导大鼠糖尿病肾病动物模型[J].山西医药杂志(上半月),2010,39(1):27-28. 被引量:6
  • 2Chow FY, Nikolic-Paterson DJ, Ozols E, et al. Monocyte chemoattractant protein-1 promotes the development of diabetic renal injury in streptozotocin-treated mice[J]. KidneyInt,2006,69(1):73-80.
  • 3Wada T, Furuiehi K, Sakai N, et al. Up-regulation of monocyte chemoattraetant protein-1 in tubulointerstitial lesions of human diabetic nephropathy [ J ]. Kidney International, 2000, 58 ( 4 ) :1492-1499.
  • 4Ha H, Yu MR, Choi YJ, et aI. Role of high glucose-induced nuclear factor-kb activation in monocyte chemoattractant protein-1 expression by mesangial cells[J]. J Am Soc Nephrol,2002,13(4):894-902.
  • 5I.i L, Emmett N, Mann D, et al. Fenofibrate attenuates tubulointerstitial fibrosis and inflammation through suppression of nuclear factor-κB and transforming growth{actor-β1/Smad3 in diabetic nephropathy[-J]. Exp Biol Med (Maywood) ,2010,235(3) :383-391.
  • 6Vaidyal VS,Niewczas MA, Fieociello LH, et al. Regression of microalbuminuria in type t diabetes is associated with lowerlevels of urinary tubular injury biomarkers, kidney injury molecule-l,and N-acetyl-β-D-glucosaminidase[J]. Kidney Int, 2011,79(4) :464-470.
  • 7孙铭柱,徐曼,邹万忠.肾小管间质纤维化中转化生长因子β1的表达特征[J].中华肾脏病杂志,2000,16(5):291-295. 被引量:25
  • 8Cutolo M, Sull Ai, Ghiorzo P, et al. Anti-inflammatory effects of leflunomide on cultured synovial macrophages from patients with rheumatoid arthritis[J].Ann Rheum Dis, 2003,62 (4):297-302.
  • 9刘俊平,于为民.糖尿病肾病大鼠核转录因子-κB的表达及来氟米特的干预作用[J].中国药物与临床,2009,9(1):37-40. 被引量:7
  • 10吕永曼,黄晓丽,易艳.霉酚酸酯对糖尿病大鼠肾间质细胞浸润及肾组织ICAM-1和MCP-1 mRNA表达的影响[J].中华肾脏病杂志,2006,22(9):576-577. 被引量:17

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  • 1迟继铭,徐丹,王晶,张岩岩.补脾益气升阳方对糖尿病大鼠肾组织MCP-1mRNA表达的影响[J].中医药学报,2009,37(4):28-32. 被引量:5
  • 2张路霞,王梅,王海燕.慢性肾脏病的流行病学研究[J].中华肾脏病杂志,2005,21(7):425-428. 被引量:69
  • 3张永,罗昌霞,张建鄂,李涛.来氟米特活性代谢产物对肿瘤坏死因子-α诱导肾小管上皮细胞内核因子-κB活性的影响[J].微循环学杂志,2006,16(2):18-20. 被引量:8
  • 4Luis -Rodriguez D, Martinez -Castelao A, G6rriz JL, et al. Pathophysiolog - ical role and therapeutic implications of inflam- mation in diabetic nephropathy. World J Diabetes ,2012,3 (1) :7 -18.
  • 5Wu CC, Sytwu HK, Lin YF. Cytokines in diabetic nephropathy. Adv Clin Chem,2012,56( 1 ) :55 -74.
  • 6Najafian B, Alpers CE, Fogo AB. Pathology of human diabetic ne- phropathy. Contrib Nephrol,2011,170 ( 1 ) :36 - 47.
  • 7Shimizu H, Bolati D, Higashiyama Y, et al. Indoxyl sulfate upreg- ulates renal expression of MCP - 1 via production of ROS and ac- tivation of NF - KB, p53, ERK, and JNK in proximal tubular ceils. Life Sci,2012,90( 13 - 14) :525 -530.
  • 8Soetikno V, Sari FR, Veeraveedu PT, et al. Curcumin ameliorates macrophage infiltration by inhibiting NF - KB activation and proinflammatory cytokines in streptozotocin induced - diabetic nephropathy. Nutr Metab (Lond) ,2011,8 ( 1 ) : 35.
  • 9Giunti S, Tesch GH, Pinach S, et al. Monocyte chemoattractant protein - 1 has prosclerotic effects both in a mouse model of ex- perimental diabetes and in vitro in human mesangial cells. Diabe- tologia,2008,51 ( 1 ) : 198 - 207.
  • 10Bhattacharya S, Manna P, Gachhui R, et al. d - Saccharic acid 1, 4 -lactone protects diabetic rat kidney by ameliorating hypergly- cemia- mediated oxidative stress and renal inflammatory cyto- kines via NF - KB and PKC signaling. Toxicol Appl Pharmacol, 2012,267(1) :16 -29.

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