Wada Ryuichi, Yagihashi Soroku
Department of Pathology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562 Japan.
Ann N Y Acad Sci. 2005 Jun;1043:598-604. doi: 10.1196/annals.1338.067.
Diabetic neuropathy is a life-threatening complication involving both peripheral and autonomic nerves. The hyperglycemia-induced polyol pathway as well as enhanced oxidative stress are among the factors implicated in the pathogenesis of diabetic neuropathy. Their effects are possibly exerted by direct nerve tissue damage or mediated by endothelial injury or vascular dysfunction. Formation of advanced glycation end product (AGE) is another important candidate for the cause of peripheral neuropathy. Indeed, the levels of AGEs were increased in the serum and also in the peripheral nerves obtained from diabetic patients. Structural and functional proteins of those nerves are also glycated, resulting in impaired nerve function and characteristic pathologic alterations. In addition, interaction between AGEs and their receptors induce biological effects on the target tissues for diabetic complications. In the peripheral nerve, the receptor for AGE (RAGE) is expressed in endothelial and Schwann cells. It is thus anticipated that interactions between AGEs and RAGE facilitate endoneural vascular dysfunction, leading to microangiopathy in the peripheral nerve. The roles of these mechanisms, in particular on the molecular mechanisms of AGE-RAGE interactions in the development of diabetic neuropathy are largely still speculative and yet to be explored.
糖尿病神经病变是一种危及生命的并发症，累及周围神经和自主神经。高血糖诱导的多元醇途径以及氧化应激增强是糖尿病神经病变发病机制中的因素。它们的作用可能是通过直接损伤神经组织或由内皮损伤或血管功能障碍介导。晚期糖基化终末产物（AGE）的形成是周围神经病变病因的另一个重要候选因素。事实上，糖尿病患者血清和周围神经中的AGE水平均升高。这些神经的结构和功能蛋白也会发生糖基化，导致神经功能受损和特征性病理改变。此外，AGE与其受体之间的相互作用会对糖尿病并发症的靶组织产生生物学效应。在周围神经中，AGE受体（RAGE）在内皮细胞和施万细胞中表达。因此，可以预期AGE与RAGE之间的相互作用会促进神经内膜血管功能障碍，导致周围神经微血管病变。这些机制的作用，特别是AGE-RAGE相互作用在糖尿病神经病变发展中的分子机制，在很大程度上仍属推测，有待进一步探索。
