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

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。

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

To investigate the protective effect of mycophenolate mofetil(MMF) on the damage in renal tubulo-interstitium 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.