The effects of aminoguanidine on retinopathy in STZ-induced diabetic rats

被引:36
作者
Luo, Dawei [1 ]
Fan, Ying [1 ]
Xu, Xun [1 ]
机构
[1] Shanghai Jiao Tong Univ, Div Ophthalmol, Affiliated Peoples Hosp 1, Shanghai 200080, Peoples R China
关键词
Diabetic retinopathy; Aminoguanidine; Advanced glycated end products (AGEs); GLYCATION END-PRODUCTS; ENDOTHELIAL GROWTH-FACTOR; CELL-DEATH; DYSFUNCTION; INHIBITION; EXPRESSION;
D O I
10.1016/j.bmcl.2012.04.130
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Background: The accumulation of advanced glycated end products (AGEs) in retinal blood vessels is one of the major etiological factors contributing to diabetic retinopathy. Aminoguanidine (AG) is one of the most extensively used inhibitors of AGEs formation. The aim of this study was to investigate whether AG could protect the development of diabetic retinopathy through inhibition of AGEs. Methods: Rat diabetes was induced by intraperitoneal injection with streptozotocin (STZ). AG was given to rats in drinking water. Retina was extracted 3 and 6 months following STZ and AG administration. Immunochemistry and transmission electron microscope were used to detect the expression of AGEs and retina morphology. Results: Extensive staining of AGEs was detected in retinal blood vessels of 3- and 6-month diabetic rats, while no significant staining was found in the control non-diabetic retina or AG treated groups. Pericyte loss, endothelial cell proliferation, increased ratio of endothelial cells/pericytes, acellular capillaries and capillary occlusion were observed in the retina of 6-month diabetic rats. The increased electron density of retinal capillary basement membrane, mitochondrial swelling in pericytes and endothelial cells were also found in 6-month diabetic rats. The 3-month diabetic rats and the AG-treated rats did not have similar morphological changes compared to control group. The AGEs staining in AG-treated rats was still weakly positive. Conclusions: AGEs plays pivotal roles in diabetic retinopathy. AGE deposition occurs prior to retinal microvasculature changes. AG could prevent the onset and development of diabetic retinopathy through inhibition of AGEs. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:4386 / 4390
页数:5
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