Department of Medicine, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Clin Sci (Lond). 2013 Oct;125(8):361-82. doi: 10.1042/CS20130065.
Oxidative stress has been linked to the pathogenesis of the major complications of diabetes in the kidney, the heart, the eye or the vasculature. NADPH oxidases of the Nox family are a major source of ROS (reactive oxygen species) and are critical mediators of redox signalling in cells from different organs afflicted by the diabetic milieu. In the present review, we provide an overview of the current knowledge related to the understanding of the role of Nox in the processes that control cell injury induced by hyperglycaemia and other predominant factors enhanced in diabetes, including the renin-angiotensin system, TGF-β (transforming growth factor-β) and AGEs (advanced glycation end-products). These observations support a critical role for Nox homologues in diabetic complications and indicate that NADPH oxidases are an important therapeutic target. Therefore the design and development of small-molecule inhibitors that selectively block Nox oxidases appears to be a reasonable approach to prevent or retard the complications of diabetes in target organs. The bioefficacy of these agents in experimental animal models is also discussed in the present review.
氧化应激与糖尿病在肾脏、心脏、眼睛或血管的主要并发症的发病机制有关。Nox 家族的 NADPH 氧化酶是 ROS（活性氧）的主要来源，是受糖尿病环境影响的不同器官细胞中氧化还原信号的关键介质。在本综述中，我们概述了目前对 Nox 在控制高血糖诱导的细胞损伤以及糖尿病中增强的其他主要因素（包括肾素-血管紧张素系统、TGF-β（转化生长因子-β）和 AGEs（晚期糖基化终产物））过程中作用的理解的相关知识。这些观察结果支持 Nox 同源物在糖尿病并发症中的关键作用，并表明 NADPH 氧化酶是一个重要的治疗靶点。因此，设计和开发选择性阻断 Nox 氧化酶的小分子抑制剂似乎是预防或延缓靶器官糖尿病并发症的合理方法。本文还讨论了这些药物在实验动物模型中的生物功效。
