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目的探讨霉酚酸酯(MMF)对糖尿病肾病大鼠肾组织转化生长因子-β1(TGF-β1)和骨调素(OPN)表达的影响和肾保护作用。方法应用链脲佐菌素(STZ)将SD大鼠制作为糖尿病肾病大鼠模型,将SD大鼠分为健康对照组(NC组)、糖尿病肾病组(DM组)和霉酚酸酯干预组(MMF组)。12周后观察24 h尿蛋白定量、血糖、肾功能、肾重/体重比,处死后采用免疫组化观察肾组织中TGF-β1、OPN的表达。结果 DM组和MMF组的尿蛋白定量、血糖、肾重/体重比较NC组明显升高,免疫组化检查TGF-β1、OPN的表达明显增加,而MMF组中TGF-β1、OPN的表达较DM组明显减少,而且TGF-β1、OPN的表达与尿蛋白、肾重/体重比成正比。结论糖尿病肾病大鼠肾组织中TGF-β1、OPN的表达明显增加;MMF对TGF-β1、OPN的表达有抑制作用;MMF可以减少蛋白尿,减轻肾小球、肾小管的硬化和纤维化,机制可能与MMF对TGF-β1、OPN表达有抑制作用相关,对糖尿病肾病有一定的治疗作用。
Objective To investigate the effects of mycophenolate mofetil (MMF) on the expression of transforming growth factor-β1 (TGF-β1) and osteopontin (OPN) in kidney of diabetic nephropathy rats. Methods SD rats were made into diabetic nephropathy rat model by streptozotocin (STZ). The SD rats were divided into healthy control group (NC group), diabetic nephropathy group (DM group) and mycophenolate mofetil intervention group (MMF group). The proteinuria, blood glucose, renal function and kidney weight / body weight ratio of 24 h were observed after 12 weeks. The expression of TGF-β1 and OPN in renal tissue was observed by immunohistochemistry after sacrificed. Results The proteinuria, blood glucose and kidney weight / body weight of DM group and MMF group were significantly higher than those of NC group. The expression of TGF-β1 and OPN was significantly increased by immunohistochemistry, while the expressions of TGF-β1 and OPN were higher in MMF than those in MMF DM group was significantly reduced, and TGF-β1, OPN expression and urinary protein, kidney weight / body weight ratio is proportional to. Conclusions The expression of TGF-β1 and OPN in diabetic nephropathy rats was significantly increased. MMF could inhibit the expression of TGF-β1 and OPN. MMF could reduce proteinuria and alleviate the glomerular and renal tubular sclerosis and fibrosis. The mechanism may be related to the inhibitory effect of MMF on TGF-β1 and OPN expression, and has a certain therapeutic effect on diabetic nephropathy.