Soulis-Liparota T, Cooper M, Papazoglou D, Clarke B, Jerums G
Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
Diabetes. 1991 Oct;40(10):1328-34. doi: 10.2337/diab.40.10.1328.
This study evaluated the relationship between the development of fluorescence related to advanced glycosylation end products (AGEs) in the kidney and experimental diabetic nephropathy over a 32-wk period. Control, untreated diabetic, and aminoguanidine-treated diabetic rats were followed for 32 wk with eight weekly measurements of urinary albumin excretion. After 32 wk, collagen-related fluorescence in aorta and kidney (whole kidney, isolated glomeruli, and renal tubules) and glomerular ultrastructure were evaluated. Diabetes was associated with a significant increase in collagen-related fluorescence in the aorta and kidney. Aminoguanidine prevented the increases in collagen-related fluorescence in aorta, isolated glomeruli, and renal tubules but not in whole kidney. Diabetes was associated with increased albuminuria, fractional mesangial volume, and glomerular basement membrane (GBM) thickness. Aminoguanidine attenuated the rise in albuminuria and prevented mesangial expansion without influencing GBM thickness in diabetic rats. The concomitant changes in collagen-related fluorescence, albuminuria, and mesangial expansion with aminoguanidine therapy are consistent with the hypothesis that AGEs may play a role in the development of diabetic nephropathy.
本研究评估了在32周的时间里，肾脏中与晚期糖基化终产物（AGEs）相关的荧光发展与实验性糖尿病肾病之间的关系。对对照组、未经治疗的糖尿病组和氨基胍治疗的糖尿病大鼠进行了32周的跟踪，每周测量一次尿白蛋白排泄量，共测量八次。32周后，评估主动脉和肾脏（全肾、分离的肾小球和肾小管）中与胶原蛋白相关的荧光以及肾小球超微结构。糖尿病与主动脉和肾脏中与胶原蛋白相关的荧光显著增加有关。氨基胍可防止主动脉、分离的肾小球和肾小管中与胶原蛋白相关的荧光增加，但不能防止全肾中的荧光增加。糖尿病与蛋白尿增加、系膜分数体积增加和肾小球基底膜（GBM）厚度增加有关。氨基胍可减轻糖尿病大鼠蛋白尿的升高，并防止系膜扩张，但不影响GBM厚度。氨基胍治疗后，与胶原蛋白相关的荧光、蛋白尿和系膜扩张的伴随变化与AGEs可能在糖尿病肾病发展中起作用的假设一致。
