Yamagishi Sho-ichi, Nakamura Kazuo, Matsui Takanori
Department of Internal Medicine III, Kurume University School of Medicine, Kurume 830-0011, Japan.
Curr Drug Discov Technol. 2006 Mar;3(1):83-8. doi: 10.2174/157016306776637555.
Vascular complications are a leading cause of blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. There is a growing body of evidence that formation and accumulation of advanced glycation end products (AGEs) progress during normal aging, and at an extremely accelerated rate in diabetes, thus being involved in the pathogenesis of diabetic vascular complications. Furthermore, the interaction by AGEs of their receptor, RAGE, activates down-stream signaling and evokes inflammatory responses in vascular wall cells. Therefore, inhibition of AGE formation or blockade of the RAGE signaling may be a promising target for therapeutic intervention to prevent diabetic vascular complications. This review discusses the molecular mechanisms of diabetic retinopathy, especially focusing on the AGE-RAGE system. Several types of inhibitors of the AGE-RAGE system and their therapeutic implications are also reviewed here.
血管并发症是导致失明、终末期肾衰竭、多种神经病变以及加速动脉粥样硬化的主要原因，这些并发症可导致糖尿病患者出现残疾和高死亡率。越来越多的证据表明，晚期糖基化终末产物（AGEs）在正常衰老过程中逐渐形成和积累，而在糖尿病患者中其形成和积累速度极快，因此参与了糖尿病血管并发症的发病机制。此外，AGEs与其受体RAGE的相互作用会激活下游信号传导，并在血管壁细胞中引发炎症反应。因此，抑制AGE的形成或阻断RAGE信号传导可能是预防糖尿病血管并发症的一种有前景的治疗干预靶点。本文综述了糖尿病视网膜病变的分子机制，尤其关注AGE-RAGE系统。本文还综述了几种AGE-RAGE系统抑制剂及其治疗意义。
