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

评估醛糖还原酶连接机制在 糖尿病对晶状体中介体和能量代谢的影响 并对结构不同的ARI和ARI进行比较评估 关于老年人代谢失衡的SDI，实验在 大鼠，分为对照组和糖尿病组。糖尿病组 包括接受/不接受两种ARI之一治疗的10天糖尿病大鼠 以及用或不用SDI治疗的4、7和10天糖尿病大鼠。 葡萄糖、糖酵解中间体、(-甘油磷酸(GP)、 和腺嘌呤核苷酸的荧光分光光度测定法。 通过酶处理的单个镜片；山梨醇的水平， 用GC/MS对果糖和肌醇进行了定量。 山梨醇与糖尿病大鼠肌醇耗竭的关系 基本上可以通过托瑞司他预防，完全可以通过 山梨醇。两种ARI均可预防关键糖酵解水平的下降 中间体和游离胞浆NAD+/NADH比率以及 糖蛋白蓄积和能量代谢障碍。全 糖尿病引起的晶状体中间代谢改变是介导的 通过醛糖还原酶参与的机制，并通过 结构不同的ARI。肌醇和肌醇的进一步消耗 GSH以及对糖酵解的不利而不是有益的影响 能量代谢是通过加强渗透胁迫来实现的，这是由于 山梨醇脱氢酶抑制，尽管改善了 镜头氧化还原状态。

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.