Devangelio Eleonora, Santilli Francesca, Formoso Gloria, Ferroni Patrizia, Bucciarelli Loredana, Michetti Noemi, Clissa Cristina, Ciabattoni Giovanni, Consoli Agostino, Davì Giovanni
Center of Excellence on Aging and Departments of Medicine and Drug Sciences, University of Chieti "G. D'Annunzio" Schools of Medicine and Pharmacy, 66013 Chieti, Italy.
Free Radic Biol Med. 2007 Aug 15;43(4):511-8. doi: 10.1016/j.freeradbiomed.2007.03.015. Epub 2007 Mar 24.
Advanced glycation end products (AGEs) contribute to diabetic vascular complications by engaging the AGE receptor (RAGE). A soluble RAGE form (sRAGE) acts as a decoy domain receptor, thus decreasing AGE cellular binding. A cross-sectional comparison of sRAGE, asymmetric dimethylarginine (ADMA) plasma levels (index of endothelial dysfunction), and urinary 8-iso-prostaglandin (PG)F(2alpha) (marker of oxidative stress) was performed between 86 diabetic patients and 43 controls. Plasma sRAGE levels were significantly lower and ADMA levels were significantly higher in diabetic patients as compared to controls (P<0.0001). HbA1c and urinary 8-iso-PGF(2alpha) were correlated inversely with sRAGE and directly with ADMA. On multivariate analysis HbA1c was independently related to sRAGE levels in diabetic patients. Twenty-four of 86 patients with newly diagnosed diabetes and 12 patients in poor metabolic control were reevaluated after treatment with a hypoglycemic agent or insulin, respectively. Improvement in metabolic control by oral agents or insulin resulted in a significant increase in sRAGE and decrease in ADMA levels (P<0.0001). Thus, poor glycemic control reduces sRAGE levels, in association with enhanced oxidative stress and endothelial dysfunction in diabetes. These abnormalities are susceptible to modulation by improvement in metabolic control.
晚期糖基化终末产物（AGEs）通过与AGE受体（RAGE）结合，导致糖尿病血管并发症。可溶性RAGE形式（sRAGE）作为一种诱饵结构域受体，从而减少AGE与细胞的结合。对86例糖尿病患者和43例对照者进行了sRAGE、不对称二甲基精氨酸（ADMA）血浆水平（内皮功能障碍指标）和尿8-异前列腺素（PG）F2α（氧化应激标志物）的横断面比较。与对照组相比，糖尿病患者的血浆sRAGE水平显著降低，ADMA水平显著升高（P<0.0001）。糖化血红蛋白（HbA1c）和尿8-异PGF2α与sRAGE呈负相关，与ADMA呈正相关。多因素分析显示，在糖尿病患者中，HbA1c与sRAGE水平独立相关。86例新诊断糖尿病患者中的24例和12例代谢控制不佳的患者分别接受降糖药物或胰岛素治疗后进行了重新评估。口服药物或胰岛素改善代谢控制后，sRAGE显著升高，ADMA水平显著降低（P<0.0001）。因此，血糖控制不佳会降低sRAGE水平，同时伴有糖尿病患者氧化应激增强和内皮功能障碍。这些异常情况可通过改善代谢控制来调节。
