Effects of inhibition of glycation and oxidative stress on the development of diabetic nephropathy in rats.

    We investigated whether aminoguanidine (AG), an inhibitor of advanced glycated end product formation, or probucol (PB), a free radical scavenger, could influence signs of glomerular and distal tubular function and morphological changes in kidneys of male Wistar rats after 6 months of streptozocin (STZ)-induced diabetes. Diabetic rats had a higher kidney weight/body weight ratio (P<.001), but neither AG nor PB influenced the increased ratio. Diabetes caused an increased urinary albumin excretion (P<.05), which was normalized by AG, but further exaggerated by PB (P<.001). Diabetes also caused an increase in the urinary excretion of Tamm-Horsfall protein (P<.001). Both AG and PB attenuated this increase (P<.05 for both). A few glomeruli displayed focal thickening of varying degrees. Silver staining disclosed the glomerulopathy to be intercapillary glomerulosclerosis. Rats on PB-enriched diet displayed less pronounced changes than untreated rats (P<.01), while AG had no effect. The results suggest that oxidative stress could be involved in the development of diabetic nephropathy.（J Diabetes Complications. 2002 Nov-Dec;16(6):395-400.）

    目的：研究高级糖基化种产物生成抑制剂氨基胍（AG）或自由基清除剂普罗布考（PB）是否对链脲霉素导致糖尿病Wistar大鼠模型的肾小球和远端肾小管功能以及肾脏形态学变化产生影响。
    结果：AG和PB均不能影响糖尿病引起的肾脏重量/体重比值的增加； AG是尿白蛋白恢复正常能够水平，PB则能进一步降低其水平（p<0.01）； AG和PB均能削弱糖尿病引起的肾小球蛋白增加（p<0.05）； 对于糖尿病引起的肾小球病灶部位不同程度的增厚，与对照组相比，PB组无明显增厚，而AG组无影响。
    结论：氧化应激可能参与糖尿病肾病的进程。