霉酚酸酯对2型糖尿病大鼠肾组织的保护作用

The Protection on Renal Tissue by Mycophenolate Mofetil in Experimental Type 2 Diabetic Rat

目的:观察霉酚酸酯(MMF)对2型糖尿病大鼠肾组织中神经生长因子(NGF)的影响。方法:应用高糖高脂饮食加小剂量链脲佐菌素(STZ)制备2型糖尿病大鼠模型,然后分别用胰岛素、MMF及二者联合干预治疗。采用免疫组织化学技术检测各组肾小球中NGF及单核/巨噬细胞(CD68)的表达水平。结果:(1)高糖高脂饮食+小量STZ后,大鼠血糖升高,且血胰岛素水平不低。继续喂养6周后大鼠肾重/体重、内生肌酐清除率(Ccr)、尿白蛋白排泄率(UAE)等指标较正常组明显升高;(2)糖尿病组大鼠肾组织中NGF、CD68表达较正常组明显增加。治疗6周后,MMF+胰岛素组NGF表达水平显著降低,单核/巨噬细胞浸润减轻,肾功能指标及组织病理学损害明显改善。结论:(1)糖尿病模型建立后6周,已出现糖尿病肾病早期改变;(2)2型糖尿病大鼠肾组织中NGF过量表达,MMF的肾脏保护作用可能与减少肾组织中NGF表达,减轻单核/巨噬细胞的浸润有关;(3)同时应用MMF和胰岛素能增强对2型糖尿病大鼠肾脏的保护作用,这可能与MMF抗炎和胰岛素降血糖双重保护作用有关。

Objective： To establish a rat model of type 2 diabetes, and to investigate the effect of mycophenolate mofetil（MMF） on renal nerve growth factor in type 2 diabetic rat. Methods：The rats of model groups were intraperitoneally injected with low- dose of streptozotocin（STZ, 30 mg/kg） after having sucrose- and fat - enriched diets（20% sucrose, 10% pig fat, 2.5% cholesterol） for one month. Subsequently, rats were treated by insulin, MMF, or both. Immuohistochemistry was used to measure the expression of nerve growth factor and monocyte/rnacrophage（CD6s） in renal tissue. Resuits： （ 1 ）Blood glucose increased by sucrose - and fat - enriched diets. Early changes of diabetic nephropathy（DN） were present in the model by 6 weeks. Kidney/weight, Ccr, UAE significantly increased. （2）Compared to normal group, the expres- sion of nerve growth factor and CD6s increased in glomeruli of experimental type 2 diabetic rat. MMF significantly inhibited the expression of nerve growth factor, ameliorated monocyte/rnacrophage infiltration, partly improved renal function and matrix accumulation. Conclusion： （ 1 ）Renal nerve growth factor greatly increases in experimental type 2 diabetic rat. The protection of MMF on kidney is associated, at least in part, with down - regulation of the expression of nerve growth factor and monocyte/macrophage recruitment in renal tissue. （2） The role of MMF, in addition to insulin, is more protective than the MMF or insulin alone on renal tissue. This protection is associated with two ways of anti - inflammation of MMF and reduced blood glucose by insulin.