霉酚酸酯对实验性1型糖尿病大鼠早期肾脏损害的保护作用研究

Preventive effect of mycophenolate mofetil on early diabetic nephropathy in a rat model

目的研究霉酚酸酯对糖尿病大鼠早期肾脏损害的保护作用，并对可能的机制进行探讨。方法雄性Wistar大鼠84只，随机分为3组：单肾切除对照组（24只），模型组（30只）和霉酚酸酯治疗组（30只）。分别于糖尿病成模后2周、4周、8周处死，观察内生肌酐清除率、24h尿微量白蛋白排泄量、肾脏病理组织学改变及巨噬细胞和淋巴细胞的浸润情况。结果模型组内生肌酐清除率增高，出现进行性微量白蛋白尿，与对照组差异有统计学意义。霉酚酸酯治疗组，内生肌酐清除率8周时明显低于模型组[（4．0263±0．8784）ml·min^-1·kg^-1vs（7．3270±2．9445）ml·min^-1·kg^-1，P〈0．05]，24h尿微量白蛋白排泄量则于各时段均低于模型组（P〈0．05），肾小球基底膜增厚较模型组明显减轻，肾小球承膜区面积占肾小球面积的比值也减小．8周时肾小球区域巨噬细胞浸润较模型组减少[（4．07±2．05）cells／ges vs（7．29±2．14）cells／gcs，P〈0．05）]，而对照组几乎未检测到。结论霉酚酸酯对糖尿病大鼠早期肾脏损害有保护作用，其机制可能是通过其抗炎、抗增殖作用产生。

Objective To investigate the protective effect of mycophenolate mofetil （MMF） on early stage renal lesions in experimental diabetic rats and to explore its mechanism. Methods Male Wistar rats were randomly divided into three groups after uninephrectomy： C, a control group（ n =24） ; DM（ n =30）, diabetic rats model with streptozotocin; DM ＋MMF（ n =30）, diabetic rats treated with MMF, 10mg/ kg once daily by garage. Creatinine clearance and urinary albumin excretion were measured at 2 weeks, 4 weeks and 8 weeks after treatment. Renal pathological changes and the infiltration of macrophages and lymphocytes in the kidney were evaluated at 8 weeks. Reset Compared with DM group, urinary albumin excretion in DM ＋ MMF group was markedly decreased at 8 weeks （ DM ： 146. 2833 ＋ 64. 29441μg/24h, vs DM ＋ MMF ：53. 59 ± 16. 3928μg/24h, P 〈0.05）, so was Creatinine clearance（ DM ： 7. 3270 ± 2. 9445 ml · min^-1· kg^- 1 vs DM ＋ MMF： 4. 0263 ± 0. 8784 ml · min^-1·kg^-1, P 〈0. 05）. Pathohistological study revealed that MMF inhibited the diabetes-induced expansion of mesangial area and thickening of GBM. The kidneys of diabetic rats exhibited marked macrophage infiltrations at 8 weeks and MMF treatment prevented macrophage infiltrations significantly （ DM ：7. 29 ± 2. 14 cells/gcs vs DM ＋ MMF ：4. 07 ± 2. 05cells/gcs, P 〈 0. 05）. Conelusion MMF may prevent the progression of diabetic nephropathy through its anti-proliferative and anti-inilammatory properties.