霉酚酸酯对糖尿病大鼠肾小管-间质损伤的保护作用及机制  

The protective effect of mycophenolate mofetil on the damage in renal tubulo-interstitium of diabetic rats and its mechanism of action

作　　者：张炜[1] 吴永贵[1] 方芳[1] 董婧[1] 任克军[1] 齐向明[1] 梁超[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：《现代免疫学》2007年第6期465-469,共5页Current Immunology

基　　金：安徽省自然科学基金资助项目(070413100);安徽省教育厅自然科学基金资助项目(2006KJ316B)

摘　　要：研究霉酚酸酯(MMF)对糖尿病大鼠肾小管-间质损伤的保护作用,并探讨其可能机制。应用链脲佐菌素诱导大鼠糖尿病模型,随机分三组:对照组、模型组与MMF给药组。8周后观察尿白蛋白排泄率(AER)、肾小管-间质病理形态学变化,应用免疫组化方法检测肾小管-间质骨桥蛋白(OPN)与α-平滑肌肌动蛋白(-αSMA)蛋白表达,Western印迹检测肾组织IL-1与TNF-α蛋白表达。结果表明,糖尿病大鼠AER与肾小管-间质损伤指数(TII)明显高于对照组(P<0.01),MMF给药组AER与TII明显低于模型组(P<0.05);免疫组化显示模型组肾小管-间质OPN与-αSMA表达阳性面积明显高于对照组(P<0.01),MMF给药组肾小管OPN与与-αSMA表达阳性面积明显低于模型组(P<0.01);Western印迹显示模型组肾组织IL-1与TNF-α表达较对照组分别增加2.8倍与3.8倍,MMF给药组IL-1与TNF-α表达分别下降73%与70%(P<0.01)。研究显示MMF对糖尿病肾小管-间质损伤有明显保护作用,其机制可能部分与抑制肾小管-间质OPN与-αSMA表达有关。To investigate the protective effect of mycophenolate mofetil（MMF） on the damage in renal tubulo-intcrstitium of diabetic rats and to explore its mechanism of action, diabetic model of rats was induced by injection of rats with streptozotocin. These diabetic rats were divided randomly into 3 groups： control, model and MMF-treated groups. Eight weeks later, the albumin excretion rate（ AER） was determined, patho-morphological changes in tubulo-interstitium were observed, and the expressions of osteopontin（OPN） and α-smooth muscle actin （α-SMA）in renal tubulo-interstitium were detected by immunohistochemical assay Western blot assay was used to demonstrate the expression of IL-1 and TNF-α protein in tubulo-interstitium. It was demonstrated that the AER and the tubulo-interstitium damage index（TII）were significantly higher than those of the control group （P〈0.01）, however, AER and TII in the MMF-treated group were significantly lower than those of the model group（P〈0. 05）. As demonstrated by the immunohistochemical assay, the positive area of expressions of OPN and α-SMA in tubulo-interstitium were comparatively larger than those in the control group（P〈0.01）, but those in the MMF-trated group were significantly lower than those in the model group（P〈0.01）. As demonstrated by Western blot assay, the expressions of IL-1 and TNF-α in tubulo-intersttium of the model group increased to 2.8 and 3.8 times in comparison with those of the control group, and reduced to 74% and 70% in the MMF-treated group（P〈 0.01 ）. It is evident that MMF can prevent the development of renal tubulo-interstitium damage in diabetic rats, and its mechanism of action may be at least partly correlated with the suppression of increased expression of OPN and α-SMA.

关 键 词：糖尿病肾病 霉酚酸酯 肾小管-间质 骨桥蛋白 Α平滑肌肌动蛋白 

分 类 号：R692.02[医药卫生—泌尿科学]