DIFFERENT ARIS (TOLRESTAT & SORBINIL) VS SDI ON DIAB INDUCED LENS METAB CHANGES

评价醛糖还原酶相关机制在 糖尿病引起的透镜介质和能量代谢的变化 并对结构不同的阿里斯与 SDI对老年人代谢失衡的影响，实验在 大鼠，分为对照组和糖尿病组。 糖尿病各组 包括用/不用两种阿里斯之一治疗的10天糖尿病大鼠 以及用/不用SDI治疗的4天、7天和10天糖尿病大鼠。 葡萄糖、糖酵解中间体、β-甘油磷酸（GP）、 和腺嘌呤核苷酸进行荧光分光光度测定， 通过酶促程序的单个镜片;山梨醇的水平， 果糖和肌醇通过GC/MS定量。 山梨糖醇和消耗的肌醇在糖尿病大鼠， 基本上被托司他阻止，并被完全阻止， 山梨醇。 两种阿里斯都能防止关键糖酵解酶水平的降低， 中间体和游离胞质NAD+/NADH比率以及 GP蓄积和能量代谢受损。 所有 糖尿病诱导的透镜中间代谢的变化是由 通过醛糖还原酶参与的机制， 结构上不同的阿里斯。 进一步消耗肌醇， GSH以及对糖酵解的不利而非有益作用， 能量代谢通过渗透胁迫的增强来实现， 山梨醇脱氢酶抑制，尽管改善了 透镜氧化还原状态。

To evaluate the role for aldose reductase-linked mechanisms in diabetes-induced changes in lens intermediary and energy metabolism and to make a comparative evaluation of structurally different ARIs vs SDI on elderly metabolic imbalances, experiments were performed on rats, divided into control and diabetic groups. Diabetic groups included 10-day diabetic rats treated with/without one of the two ARIs as well as 4-,7-, and 10-day diabetic rats treated with/without SDI. Levels of glucose, glycolytic intermediates, (-glycerophosphate (GP), and adenine nucleotides were assayed spectrofluorometrically in individual lenses by enzymatic procedures; levels of sorbitol, fructose, and myo-inositol were quantified by GC/MS. Accumulation of sorbitol and the depletion of myo-inositol in diabetic rats were substantially prevented by tolrestat and were completely prevented by sorbinil. Both ARIs prevented decreases in levels of key glycolytic intermediates and free cytosolic NAD+/NADH r atios as well as accumulation of GP and impairment of energy metabolism. All diabetes-induced changes in lens intermediary metabolism are mediated by aldose reductase-involved mechanisms and are prevented by structurally different ARIs. Further depletion of myo-inositol and GSH as well as adverse rather than beneficial effect on glycolysis and energy metabolism is achieved by potentiation of osmotic stress due to sorbitol dehydrogenase inhibition in spite of an improvement of the lens redox state.