来氟米特对大鼠肾毒血清性肾炎早期肾损害的保护作用  

Protective effect of leflunomide on experimental nephrotoxic serum nephritis

作　　者：赵珉[1] 张伯科[1] 王坤[1] 钱浩[1] 戴宏[1] 梁维龙[1] 阚春明[1] 

机构地区：[1]安徽医科大学第一附属医院肾脏内科,合肥230022

出　　处：《安徽医科大学学报》2006年第3期290-293,共4页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金资助项目(编号:04023051)

摘　　要：目的探讨来氟米特(LEF)对大鼠肾毒血清性肾炎早期肾损害的保护作用。方法建立大鼠肾毒血清肾炎模型,随机分为正常对照组、病理对照组、LEF干预组(5mg/kg/d,灌胃)。2周末检测24h尿蛋白含量、血清学指标;观察肾小球病理形态及免疫组化变化。结果病理对照组24h尿蛋白水平明显高于正常对照组(P<0·01),血浆白蛋白水平明显低于正常对照组(P<0·05),肾小球内细胞数、含新月体肾小球数、硬化肾小球数、肾组织中MCP-1、ED1+细胞浸润明显高于正常对照组(P<0·05)。肾组织中ED1+细胞数与尿蛋白排泄量、形成新月体的肾小球百分数呈显著正相关(P<0·01),形成新月体的肾小球百分数与尿蛋白排泄量亦呈显著正相关(P<0·01)。LEF干预组大鼠尿蛋白水平、肾小球细胞总数、硬化肾小球数、新月体数、肾小球ED1+细胞浸润及MCP-1表达均明显低于病理对照组(P<0·01,0·05)。结论LEF能改善肾毒血清性肾炎大鼠早期肾脏病变,其机制可能部分与抑制肾组织MCP-1表达和巨噬细胞浸润有关。Objective To investigate the effect of novel immunosuppressive agents, leflunomide, on nephrotoxic serum nephritis in rats. Methods SD rats were randomly divided into three groups： control group, model group, LEF（5 mg/kg/d, by garage）treatment group. The nephrotoxic serum nephritis was induced using injection of rabbit anti-rat GBM antibody into the tail veins of the rats. The effects of daily treatment of LEF from 6 hours after injection of the rabbit antiserum to day 14 on proteinuria, serum parameters and glomerular alterations were analyzed. Results Compared with the control group, increased excretion of proteinuria （P 〈 0. 01 ）, hypoproteinemia （P 〈 0. 05 ）, glomerular hypercellularity, crescent formation and nephrosclerosis （ P 〈0. 01 ） were observed in the nephritic rats ; significant up-regulation of MCP-1 expression and infilitration of macrophages （ P 〈 0. 05 ） were also observed in glomeruli. The amount of urinary protein and the percentage of crescentic glomeruli correlated significanfly with the numbers of glomerular ED1 ＋ cells （ P 〈 0. 01 ）. There was also a stronger correlation between the percentage of crescentic glomeruli and the amount of urinary protein （P 〈0. 01 ）. LEF significantly decreased urinary protein excretion, glomerular hypercellularity, crescents （P 〈 0. 01 ）, as well as expression of MCP-1 and infilitration of macrophages in glomeruli （ P 〈 0. 05 ）. Conclusion Leflunomide can inhibit the progression of rat nephrotoxic serum nephritis. Its renoprotective mechanism may be, at least partly, correlated with inhibition MCP- 1 overexpression and macrophage infiltration in renal tissue of nephritic rats.

关 键 词：肾小球肾炎/药物疗法 异恶唑类/药理学 单核细胞化学吸引蛋白1/分析 巨噬细胞 

分 类 号：R692.31[医药卫生—泌尿科学] R979.5[医药卫生—外科学]