Kojima K, Matsubara H, Harada T, Mizuno K, Suzuki M, Hotta N, Kakuta H, Sakamoto N
Jpn J Ophthalmol. 1985;29(1):99-109.
Wistar strain rats were made diabetic by injection of streptozotocin and divided into three groups fed on different diets: conventional solid foods, a fructose-rich diet and a fructose-rich diet mixed with ONO 2235, an aldose reductase inhibitor. The retinas of these rats were examined in flat mount preparations after trypsinization. Microvascular changes such as capillary tortuosity, microaneurysms, pericyte loss, that are typical of diabetic retinal microangiopathy, were seen most frequently in the rats fed on the fructose-rich diet. The rats fed on the fructose-rich diet with ONO 2235 showed much less vascular change than the diabetic rats fed on the conventional food. Electron microscopy of the retina revealed localized thickening of the basement membrane of the retinal capillaries, and this was most frequent in the fructose-fed rats. However, in rats fed on fructose with ONO 2235 the changes of the basement membrane were slight. It was concluded that the aldose reductase inhibitor, ONO 2235, prevented development of diabetic microangiopathy, probably by suppressing the enzymatic activation of aldose reductase in the retina.
通过注射链脲佐菌素使Wistar品系大鼠患糖尿病，并将其分为三组，分别喂食不同的饮食：常规固体食物、富含果糖的饮食以及富含果糖且混有醛糖还原酶抑制剂ONO 2235的饮食。胰蛋白酶消化后，在平铺标本中检查这些大鼠的视网膜。糖尿病视网膜微血管病变的典型微血管变化，如毛细血管迂曲、微动脉瘤、周细胞丢失，在喂食富含果糖饮食的大鼠中最为常见。喂食富含果糖且含有ONO 2235的饮食的大鼠，其血管变化比喂食常规食物的糖尿病大鼠少得多。视网膜的电子显微镜检查显示视网膜毛细血管基底膜局部增厚，这在喂食果糖的大鼠中最为常见。然而，在喂食含有ONO 2235的果糖的大鼠中，基底膜的变化很轻微。得出的结论是，醛糖还原酶抑制剂ONO 2235可能通过抑制视网膜中醛糖还原酶的酶促活化，预防糖尿病微血管病变的发展。
