Kador P F, Inoue J, Secchi E F, Lizak M J, Rodriguez L, Mori K, Greentree W, Blessing K, Lackner P A, Sato S
Laboratory of Ocular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Exp Eye Res. 1998 Aug;67(2):203-8. doi: 10.1006/exer.1998.0502.
Several recent studies with the sorbitol dehydrogenase inhibitors 4-[4-(N,N-dimethylsulfamoyl)-piperazino]-2-methylpyrimidine, SDH-1, and its active metabolite 4-[4-(N, N-dimethylsulfamoyl)piperazino]-2-hydroxymethylpyrimidine , SDH-2, suggest that inhibition of sorbitol dehydrogenase may be beneficial in delaying the onset of diabetic complications due to their ability to ameliorate redox changes associated with polyol metabolism. To compare the relative importance of sorbitol dehydrogenase versus aldose reductase inhibition on sugar cataract formation, cataract formation was monitored in 50% galactose-fed and diabetic rats treated with/without the sorbitol dehydrogenase inhibitors SDH-1 or SDH-2 or the aldose reductase inhibitors AL 1576 or Ponalrestat. For these studies, diabetes was induced in young 50 g rats with streptozotocin while galactosemia was produced by feeding a diet containing 50% galactose. Inhibitors were administered in the diet with the diet containing 0.06% (w/w) of the sorbitol dehydrogenase inhibitors or Ponalrestat, and 0.0125% (w/w) of AL 1576. Cataract formation was monitored by hand-held slit lamp and polyol levels were measured by gas chromatography. Sugar cataract formation was accelerated in diabetic rats treated with sorbitol dehydrogenase inhibitors while no difference in cataract formation was observed in galactose-fed rats treated with/without SDH inhibitors. Cataract formation was inhibited in both diabetic and galactosemic rats by either Ponalrestat or AL 1576. These results support the concept that sugar cataract formation is initiated by the aldose reductase catalysed intracellular accumulation of polyols and that these sugar cataracts can be prevented through inhibition of aldose reductase.
最近几项针对山梨醇脱氢酶抑制剂4-[4-(N,N-二甲基氨磺酰基)-哌嗪基]-2-甲基嘧啶（SDH-1）及其活性代谢物4-[4-(N,N-二甲基氨磺酰基)哌嗪基]-2-羟甲基嘧啶（SDH-2）的研究表明，抑制山梨醇脱氢酶可能有助于延缓糖尿病并发症的发生，因为它们能够改善与多元醇代谢相关的氧化还原变化。为了比较山梨醇脱氢酶抑制与醛糖还原酶抑制在糖性白内障形成中的相对重要性，对喂食50%半乳糖的大鼠和糖尿病大鼠进行了监测，这些大鼠分别接受/未接受山梨醇脱氢酶抑制剂SDH-1或SDH-2或醛糖还原酶抑制剂AL 1576或泊那司他的治疗。在这些研究中，用链脲佐菌素诱导50 g幼鼠患糖尿病，同时通过喂食含50%半乳糖的饮食产生半乳糖血症。抑制剂与含0.06%（w/w）山梨醇脱氢酶抑制剂或泊那司他以及0.0125%（w/w）AL 1576的饮食一起给予。通过手持裂隙灯监测白内障的形成，并通过气相色谱法测量多元醇水平。用山梨醇脱氢酶抑制剂治疗的糖尿病大鼠中糖性白内障的形成加速，而在接受/未接受SDH抑制剂治疗的喂食半乳糖的大鼠中未观察到白内障形成的差异。泊那司他或AL 1576均可抑制糖尿病大鼠和半乳糖血症大鼠的白内障形成。这些结果支持了这样一种观点，即糖性白内障的形成是由醛糖还原酶催化的细胞内多元醇积累引发的，并且这些糖性白内障可以通过抑制醛糖还原酶来预防。
