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β1表达的影响

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。

Effect of leflunomide on renal expression of monocyte chemoattractant protein-1 and transforming growth factor-beta 1 in diabetic nephropathy rats

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.