醛糖还原酶抑制剂索比尼尔对正常及链脲佐菌素诱导的糖尿病大鼠主动脉功能的影响。

The effect of sorbinil, an aldose reductase inhibitor, on aortic function in control and streptozotocin-induced diabetic rats.

Sellers D J, Chess-Williams R

Department of Biomedical Science, University of Sheffield, Western Bank, UK.

J Auton Pharmacol. 2000 Feb;20(1):15-22. doi: 10.1046/j.1365-2680.2000.00155.x.

Abstract

The present study investigates the effect of treatment of 14-day streptozotocin-diabetic rats with the aldose reductase inhibitor, sorbinil, on changes ex vivo in aortic vasoconstriction and vasodilation. 2. Maximum contractile responses and aortic sensitivity to phenylephrine were significantly enhanced in aortae from 14-day diabetic rats, in accordance with our previous data. 3. Endothelium-dependent relaxations to carbachol were, in contrast, depressed, although endothelium-independent relaxations to forskolin and sodium nitroprusside were unaltered. 4. Sorbinil treatment of diabetic animals failed to prevent any of these diabetes-induced alterations in aortic function, and indeed exacerbated some of these alterations. In addition, sorbinil treatment caused altered aortic responses in control animals, which sometimes mirrored those found in diabetic animals. 5. It can be concluded that sorbinil may have actions in addition to, and independent of, polyol pathway inhibition. Thus, sorbinil may not be an effective tool for the investigation of aldose reductase inhibition within the vascular system of the rat.

摘要

本研究调查了用醛糖还原酶抑制剂索比尼尔治疗14天链脲佐菌素诱导的糖尿病大鼠对主动脉血管收缩和舒张离体变化的影响。2. 与我们之前的数据一致，14天糖尿病大鼠主动脉的最大收缩反应和对去氧肾上腺素的敏感性显著增强。3. 相比之下，对卡巴胆碱的内皮依赖性舒张受到抑制，尽管对福斯可林和硝普钠的非内皮依赖性舒张未改变。4. 用索比尼尔治疗糖尿病动物未能预防这些糖尿病诱导的主动脉功能改变中的任何一种，实际上还加剧了其中一些改变。此外，索比尼尔治疗导致对照动物的主动脉反应改变，这些改变有时与糖尿病动物中发现的改变相似。5. 可以得出结论，索比尼尔可能除了抑制多元醇途径外还有其他作用，且这些作用是独立的。因此，索比尼尔可能不是研究大鼠血管系统中醛糖还原酶抑制作用的有效工具。