Hammes H P, Martin S, Federlin K, Geisen K, Brownlee M
III. Medizinische Klinik, Justus-Liebig-Universität, Giessen, Federal Republic of Germany.
Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11555-8. doi: 10.1073/pnas.88.24.11555.
Retinal capillary closure induced by hyperglycemia is the principal pathophysiologic abnormality underlying diabetic retinopathy, but the mechanisms by which this induction occurs are not clear. Treatment of diabetic rats for 26 weeks with aminoguanidine, an inhibitor of advanced glycosylation product formation, prevented a 2.6-fold accumulation of these products at branching sites of precapillary arterioles where abnormal periodic acid/Schiff reagent-positive deposits also occurred. Aminoguanidine treatment completely prevented abnormal endothelial cell proliferation and significantly diminished pericyte dropout. After 75 weeks, untreated diabetic animals developed an 18.6-fold increase in the number of acellular capillaries and formed capillary microaneurysms, characteristic pathologic features of background diabetic retinopathy. In contrast, aminoguanidine-treated diabetic animals had only a 3.6-fold increase in acellular capillaries and no microaneurysms. These findings indicate that advanced glycosylation product accumulation contributes to the development of diabetic retinopathy and suggest that aminoguanidine may have future therapeutic use in this disorder.
高血糖诱导的视网膜毛细血管闭塞是糖尿病视网膜病变的主要病理生理异常，但这种诱导发生的机制尚不清楚。用氨基胍（一种晚期糖基化产物形成抑制剂）对糖尿病大鼠进行26周的治疗，可防止这些产物在毛细血管前小动脉分支部位积累2.6倍，在这些部位也出现了异常的高碘酸/席夫试剂阳性沉积物。氨基胍治疗完全防止了异常的内皮细胞增殖，并显著减少了周细胞丢失。75周后，未治疗的糖尿病动物无细胞毛细血管数量增加了18.6倍，并形成了毛细血管微动脉瘤，这是背景性糖尿病视网膜病变的特征性病理特征。相比之下，氨基胍治疗的糖尿病动物无细胞毛细血管仅增加了3.6倍，且无微动脉瘤。这些发现表明晚期糖基化产物的积累促进了糖尿病视网膜病变的发展，并提示氨基胍在这种疾病中可能具有未来的治疗用途。
