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[黏附分子与糖尿病]

[Adhesion molecules and diabetes mellitus].

作者信息

Urso C, Hopps E, Caimi G

机构信息

Dipartimento di Medicina Interna, Malattie Cardiovascolari e Nefrourologiche. Università degli Studi di Palermo, Palermo, Italia.

出版信息

Clin Ter. 2010;161(1):e17-24.

Abstract

Adhesion molecules play a significant role in leukocyte migration across the endothelium and are also involved in regulating immune system. It is shown that diabetic patients have an increase of soluble adhesion molecules (sICAM-1, sICAM-2, sVCAM-1, sE-selectin, sL-selectin, sP-selectin) considered an integral part of inflammatory state. This inflammation is responsible for the increased cardiovascular risk of these patients. There is a close link between hyperglycemia, oxidative stress, coagulopathy and inflammation and between these factors and the vascular damage. Various studies have showed the potential role of adhesion molecules in the pathogenesis of diabetic vasculopathy. They promote leukocyte recruitment, which is one of the initial steps in the genesis of atherosclerotic plaque. Adhesion molecules are also involved in the pathogenesis of diabetes mellitus type 1; sICAM-1 would have a particular immunomodulatory role in the process of destroying beta-cells and could be used as a subclinical marker of insulitis. Plasma levels of soluble adhesion molecules correlate with hyperglycemia, insulin resistance, dyslipidemia and obesity; they are associated with the development of nephropathy, retinopathy, myocardial infarction, stroke and obliterant peripheral arterial disease in diabetic type 1 and 2. Given the role of these molecules in endothelial dysfunction genesis and tissue damage associated with diabetes, they could constitute a therapeutic target for the prevention of genesis and progression of chronic complications of diabetic disease.

摘要

黏附分子在白细胞跨内皮迁移中起重要作用,也参与免疫系统的调节。研究表明,糖尿病患者可溶性黏附分子(可溶性细胞间黏附分子-1、可溶性细胞间黏附分子-2、可溶性血管细胞黏附分子-1、可溶性E-选择素、可溶性L-选择素、可溶性P-选择素)增加,这些分子被认为是炎症状态的一个组成部分。这种炎症是这些患者心血管风险增加的原因。高血糖、氧化应激、凝血病与炎症之间以及这些因素与血管损伤之间存在密切联系。各种研究表明黏附分子在糖尿病血管病变发病机制中的潜在作用。它们促进白细胞募集,这是动脉粥样硬化斑块形成的初始步骤之一。黏附分子也参与1型糖尿病的发病机制;可溶性细胞间黏附分子-1在β细胞破坏过程中具有特殊的免疫调节作用,可作为胰岛炎的亚临床标志物。可溶性黏附分子的血浆水平与高血糖、胰岛素抵抗、血脂异常和肥胖相关;它们与1型和2型糖尿病患者肾病、视网膜病变、心肌梗死、中风和闭塞性外周动脉疾病的发生有关。鉴于这些分子在糖尿病相关内皮功能障碍发生和组织损伤中的作用,它们可能成为预防糖尿病慢性并发症发生和进展的治疗靶点。

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