Haslbeck K-M, Schleicher E, Bierhaus A, Nawroth P, Haslbeck M, Neundörfer B, Heuss D
Department of Neurology, University of Erlangen-Nürnberg, Germany.
Exp Clin Endocrinol Diabetes. 2005 May;113(5):288-91. doi: 10.1055/s-2005-865600.
Binding of ligands to the receptor for advanced glycation end products (RAGE) results in activation of the transcription factor nuclear factor kappa B (NF-(kappa)B) and subsequent expression of NF-(kappa)B-regulated cytokines. This has been shown to be a relevant pathomechanism in diabetic polyneuropathies (PNP). To determine whether this pathway may contribute to the pathogenesis of PNP due to impaired glucose tolerance (IGT) we performed a pilot study to demonstrate the presence of the RAGE ligand N (epsilon)-(Carboxymethyl)lysine (CML), the receptor itself and N-(kappa)B in sural nerve biopsies of 4 patients with IGT-related PNP. Biopsies of either 4 patients with diabetic PNP and with Charcot-Marie-Tooth disease (CMT) I and II served as positive and negative controls, respectively. In IGT-related PNP and diabetic PNP, CML, RAGE, and NF-(kappa)B was found in the perineurium, epineurial vessels and in part in endoneurial vessels. CMT patients showed, if any, only weak staining for one or the other antigen. These data suggest that activation of the RAGE pathway may be one of the first steps in the pathogenesis of PNP even before chronic hyperglycemia occurs.
配体与晚期糖基化终产物受体（RAGE）结合会导致转录因子核因子κB（NF-κB）活化，随后NF-κB调控的细胞因子表达。这已被证明是糖尿病性多发性神经病（PNP）的一种相关发病机制。为了确定该途径是否可能因糖耐量受损（IGT）而导致PNP的发病，我们进行了一项初步研究，以证明4例IGT相关PNP患者腓肠神经活检中RAGE配体N-ε-（羧甲基）赖氨酸（CML）、受体本身和NF-κB的存在。4例糖尿病性PNP患者以及遗传性运动感觉神经病（CMT）I型和II型患者的活检分别作为阳性和阴性对照。在IGT相关PNP和糖尿病性PNP中，CML、RAGE和NF-κB存在于神经束膜、神经外膜血管以及部分神经内膜血管中。CMT患者即使有染色，也仅对一种或另一种抗原呈弱阳性。这些数据表明，RAGE途径的激活可能是PNP发病机制中的早期步骤之一，甚至在慢性高血糖出现之前。
