目的 探讨霉酚酸酯（MMF）对糖尿病（DM）大鼠肾脏的保护作用及其机制。 方法 将实验动物分为正常对照组、DM组及MMF治疗组。MMF组给予MMF(15 mg/kg，口服，1次/d) 治疗。8 周后检测各组大鼠尿蛋白量（24 h）、内生肌酐清除率（Ccr）、血糖；HE染色观察肾脏病理改变；免疫组化及RT-PCR法检测肾组织中基质金属蛋白酶9（MMP-9）、转化生长因子β1（TGF-β1）的表达。 结果 DM组大鼠血糖[（22.18±3.36） mmol/L比（6.40±0.87）mmol/L]、尿蛋白量（24 h）[（26.80±0.82） mg比（6.64±1.42） mg]、Ccr[（0.220±0.380） ml/min比（0.098±0.015） ml/min]显著高于对照组（P ＜ 0.05）。MMF组的尿蛋白量（24 h）[（16.17±1.15） mg]、Ccr[（0.220±0.380） ml/min比（0.207±0.377） ml/min]均显著低于DM组（P ＜ 0.05）。与DM组比较，MMF组肾小球肿大、系膜细胞增生显著减轻。肾组织中MMP-9在对照组表达较多，主要在肾小球系膜细胞胞质内及肾小管上皮细胞，DM组表达较弱，MMF组介于两组之间，组间差异均有统计学意义（P < 0.05）。TGF-β1在正常对照组大鼠肾组织有少量表达，在DM组表达较强，在MMF组介于两组之间，组间差异亦均有统计学意义（P < 0.05）。 结论 MMF可降低DM大鼠尿蛋白排泄、Ccr，减轻早期肾小球肥大，此作用可能与MMF上调肾组织中MMP-9表达、下调TGF-β1的表达、减少系膜外基质的沉积有关。

Objective To evaluate the protective effects of mycophenolate mofetil (MMF) on the kidneys of diabetic rats and elucidate the associated mechanisms. Methods Wistar rats were divided into three groups: normal control rats, diabetic rats, and diabetic rats received MMF(15 mg&#8226;kg－1&#8226;d－1). Eight weeks later, 24 h urinary albumin excretion, creatine clearance rate(Ccr), and blood glucose were measured, and kidney pathology was observed. Inmmunohistochemistry and RT-PCR were used to analyze the expression of matrix metalloproteinase-9(MMP-9) and transforming growth factor β1 (TGF-β1 ). Results As compared with normal control rats, the 24 h urinary albumin excretion [(26.80±0.82) mg vs (6.64±1.42) mg], blood glucose[(22.18±3.36) mmol/L vs (6.40±0.87) mmol/L], Ccr[(0.220±0.380) ml/min vs(0.098±0.015) ml/min] of the diabetic rats were rised remarkbably. The 24 h urinary albumin excretion [(16.17±1.15) mg] and Ccr [(0.207±0.377) ml/min] of the diabetic rats received MMF were lower as compared to diabetic rats(P＜0.05). MMP-9 in renal tissue of normal control rats was mainly expressed in glomerular mesangial cells and renal tubular epithelial cells. Such MMP-9 expression was weak in diabetic rats and improved in the diabetic rats received MMF. There were significant differences among 3 groups. The expression of TGF-β1 was on the contrary. Conclusion Mycophenolate mofetil decreases 24 h urinary albumin, Ccr and glomerular volume, which may be associated with the increase of MMP-9, the decrease of TGF-β1 expression and extracellular matrix deposition in renal tissue.