Diminished proteinuria in diabetes mellitus by sorbinil, an aldose reductase inhibitor.
Diminished proteinuria in diabetes mellitus by sorbinil, an aldose reductase inhibitor.
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索宾尼尔（一种醛糖还原酶抑制剂）可减少糖尿病患者的蛋白尿。
DOI：
10.1159/000138152
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发表时间：
1986
期刊：
影响因子：
3.1
通讯作者：
Varagiannis,E
中科院分区：
文献类型：
--
作者：
Beyer-Mears,A;Cruz,E;Edelist,T;Varagiannis,E
对链脲佐菌素诱导的糖尿病大鼠，同时口服山梨醇醛糖还原酶抑制剂山梨醇可减少蛋白尿。动物被分为三组：对照组、糖尿病组和山梨比尼治疗组。在10周的时间里，每周分析24小时尿液样本的体积、葡萄糖、酮、总蛋白（Pesce-Strande）和分子量在15,000至120,000道尔顿之间的单个蛋白质成分。后者采用聚丙烯酰胺凝胶电泳检测，激光密度分析定量。结果表明，对照组分泌白蛋白（68,000道尔顿）和低分子量蛋白（15,000 - 20,000道尔顿）。在糖尿病的10周期间，24小时内尿蛋白总量增加了7- 12倍。糖尿病引起的蛋白尿主要是由于新检测到的分子量为30,000-100,000道尔顿的蛋白质的排泄和白蛋白的增加。山梨醇治疗可防止总蛋白排泄增加约70%，尽管持续高血糖、糖尿和酮尿。激光密度分析表明，醛糖还原酶抑制剂可减少70%的新检测蛋白和白蛋白的排泄，同时保持15,000至20,000道尔顿的蛋白。这些结果表明多元醇途径与糖尿病引起的蛋白尿有关，醛糖还原酶的抑制可能是糖尿病肾病的一种治疗方法。
Proteinuria was diminished by concomitant oral administration of sorbinil, an aldose reductase inhibitor to streptozotocin-induced diabetic rats. Animals were placed in one of three groups: control, diabetic, sorbinil-treated diabetic. For a period of 10 weeks, 24-hour urine samples were analyzed weekly for volume, glucose, ketone, total protein (Pesce-Strande) and individual protein components having molecular weights between 15,000 and 120,000 daltons. The latter were examined by polyacrylamide gel electrophoresis and quantitated by laser densitometric analysis. Results indicated that controls excreted albumin (68,000 daltons) and low-molecular weight proteins between 15,000 and 20,000 daltons. Throughout the 10-week period of diabetes, there was a 7- to 12-fold increase in total urinary protein excreted in 24 h. Diabetic-induced proteinuria primarily resulted from excretion of newly detected proteins having molecular weights of 30,000–100,000 daltons and an increase amount of albumin. Sorbinil treatment prevented approximately 70% of the increase in total protein excretion despite persistent hyperglycemia, glycosuria and ketonuria. Laser densitometric analysis indicated that the aldose reductase inhibitor decreased by 70% the excretion of newly detected proteins and albumin while maintaining the 15,000- to 20,000-dalton proteins. These results suggest that the polyol pathway is implicated in diabetic-induced proteinuria and inhibition of aldose reductase may represent a therapeutic approach for management of diabetic nephropathy.