他克莫司对糖尿病早期大鼠肾组织巨噬细胞浸润、增殖及活化的影响  

Effect of tacrolimus on macrophage accumulation, proliferation and activation in the kidneyof early diabetic rats

作　　者：苏双全[1] 赵莉[1] 夏林[1] 胡梅芬[1] 吴永贵[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：《中华肾脏病杂志》2012年第7期507-511,共5页Chinese Journal of Nephrology

基　　金：教育部高等学校博士学科点专项科研基金（20093420110003）;安徽省教育厅自然科学基金（2006KJ316B）

摘　　要：目的研究他克莫司（FK506）对糖尿病早期大鼠肾组织巨噬细胞浸润、增殖及活化的影响及探讨其肾脏保护作用机制。方法链脲菌素（SIZ）腹腔一次性注射建立大鼠糖尿病模型。按数字随机法分为对照组、模型组、他克莫司（0．5、1．0mg·kg^-1·d^-1）治疗组，4周后观察大鼠肾质量指数（肾质量／体质量，KWI）、尿白蛋白排泄率（UAER）、肌酐清除率（Ccr）及肾组织病理形态学变化。应用免疫组化单染及双染方法检测肾组织内巨噬细胞表面标志抗原ED．1、增殖细胞核抗原（PCNA）及诱生性一氧化氮合酶（iNOS）的表达。结果他克莫司1．0组大鼠KWI低于模型组（P〈0．05）。他克莫司0．5组与1．0组大鼠UAER水平与肾小球平均体积低于模型组（P〈0．05）。他克莫司1．0组肾小管间质损伤指数也明显低于模型组（P〈0．01）。免疫组化显示模型组大鼠肾组织ED-1＋、PCNA＋及iNOS＋巨噬细胞数显著高于对照组（P〈0．01）；他克莫司0．5与1．0组ED-1＋的巨噬细胞数与模型组差异无统计学意义；PCNA＋及iNOS＋的巨噬细胞数则显著低于模型组（P〈0．01）。结论他克莫司可改善糖尿病早期大鼠肾损害，其机制可能部分与抑制肾组织中巨噬细胞的增殖及活化有关。Objective To investigate the effect of tacrolimus （FK506） on macrophage accumulation ,proliferation and activation in the kidney of early diabetic rats and to explore its possible mechanism of renal protection. Methods Rats were randomly divided into control, model and tacrolimus groups. Diabetic model rats were induced with intraperitoneal injection of streptozotocin. Tacrolimus （0.5 or 1.0 mg·kg^-1·d^-1） was orally administered once a day for 4 weeks. Kidney weight index （KWI）, 24-h urinary albumin excretion rate （UAER） and creatinine clearance rate （Ccr） were measured. Kidney pathology was observed by light microscopy. ED-1, PCNA and iNOS positive macrophages were detected by single and double staining of immunohistochemistry. Results KWI increased in model group and was significantly reduced by tacrolimus treatment with 1.0 mg·kg^-1·d^-1 （P〈0.05）. UAER elevated in model group and was markedly attenuated by tacrolimus treatment with 0.5 and 1.0 mg·kg^-1·d^-1（P〈0.05）. Elevated glomerular volume of model rats was significantly decreased by tacrolimus treatment with 0.5 and1.0 mg·kg^-1·d^-1 （P〈0.05）, and increased indices of tubulointerstitial injury were only ameliorated by 1.0 rag·kg^-1·d^-1 tacrolimus （P〈0.01）. Marked accumulation of ED^-1 ＋ cells in diabetic kidney was found, which was not inhibited by tacrolimus treatment with 0.5 and 1.0 mg·kg^-1·d^-1. ED-1＋ PCNA＋ cells and ED-1＋ iNOS＋ cells were significantly elevated in kidneys of model group, while they were significantly inhibited by tacrolimus treatment with 0.5 and 1.0 mg·kg^-1·d^-1 （P〈0.01）. Conclusion Tacrolimus can ameliorate early renal injury of diabetic rats and its mechanism may be partly associated with the suppression of increased macrophages activation.

关 键 词：糖尿病肾病 他克莫司 巨噬细胞 增殖细胞核抗原 一氧化氮合 酶 

分 类 号：R285.5[医药卫生—中药学]