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BGP-15,一种羟肟酸衍生物,对 2 型糖尿病大鼠模型的视网膜保护作用优于格列本脲、二甲双胍和吡格列酮。

Retinoprotection by BGP-15, a Hydroximic Acid Derivative, in a Type II Diabetic Rat Model Compared to Glibenclamide, Metformin, and Pioglitazone.

机构信息

Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98., H-4032 Debrecen, Hungary.

出版信息

Int J Mol Sci. 2020 Mar 19;21(6):2124. doi: 10.3390/ijms21062124.

Abstract

High blood glucose and the consequential ischemia-reperfusion (I/R) injury damage vessels of the retina, deteriorating its function, which can be clearly visualized by electroretinography (ERG). The aim of the present study was to evaluate the possible retinoprotective effects of systemic BGP-15, an emerging drug candidate, in an insulin resistant animal model, the Goto-Kakizaki rat, and compare these results with well-known anti-diabetics such as glibenclamide, metformin, and pioglitazone, which even led to some novel conclusions about these well-known agents. Experiments were carried out on diseased animal model (Goto-Kakizaki rats). The used methods include weight measurement, glucose-related measurements-like fasting blood sugar analysis, oral glucose tolerance test, hyperinsulinemic euglycemic glucose clamp (HEGC), and calculations of different indices from HEGC results-electroretinography and Western Blot. Beside its apparent insulin sensitization, BGP-15 was also able to counteract the retina-damaging effect of Type II diabetes comparable to the aforementioned anti-diabetics. The mechanism of retinoprotective action may include sirtuin 1 (SIRT1) and matrix metalloproteinase 9 (MMP9) enzymes, as BGP-15 was able to elevate SIRT1 and decrease MMP9 expression in the eye. Based on our results, this emerging hydroximic acid derivative might be a future target of pharmacological developments as a potential drug against the harmful consequences of diabetes, such as diabetic retinopathy.

摘要

高血糖和随之而来的缺血再灌注 (I/R) 损伤会损害视网膜血管,使其功能恶化,这可以通过视网膜电图 (ERG) 清楚地观察到。本研究旨在评估全身 BGP-15(一种新兴的候选药物)在胰岛素抵抗动物模型,即 Goto-Kakizaki 大鼠中的可能的视网膜保护作用,并将这些结果与众所周知的抗糖尿病药物(如格列本脲、二甲双胍和吡格列酮)进行比较,这些结果甚至对这些知名药物提出了一些新的结论。实验在患病动物模型(Goto-Kakizaki 大鼠)上进行。使用的方法包括体重测量、与葡萄糖相关的测量,如空腹血糖分析、口服葡萄糖耐量试验、高胰岛素正葡萄糖钳夹 (HEGC),以及从 HEGC 结果中计算不同指数——视网膜电图和 Western Blot。除了明显的胰岛素增敏作用外,BGP-15 还能够对抗 II 型糖尿病对视网膜的损害,效果可与上述抗糖尿病药物相媲美。其视网膜保护作用的机制可能包括沉默信息调节因子 1 (SIRT1) 和基质金属蛋白酶 9 (MMP9) 酶,因为 BGP-15 能够提高眼睛中的 SIRT1 并降低 MMP9 的表达。基于我们的结果,这种新兴的羟肟酸衍生物可能成为药理学发展的未来目标,作为一种潜在的药物,可对抗糖尿病的有害后果,如糖尿病性视网膜病变。

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