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[糖尿病、氧化应激与晚期糖基化终产物]

[Diabetes mellitus, oxidative stress and advanced glycation endproducts].

作者信息

Bonnefont-Rousselot D, Beaudeux J-L, Thérond P, Peynet J, Legrand A, Delattre J

机构信息

Laboratoire de Biochimie métabolique et clinique (EA 3617), Faculté de Pharmacie Paris 5, 4, avenue de l'Observatoire, F75270 Paris Cedex 06.

出版信息

Ann Pharm Fr. 2004 May;62(3):147-57. doi: 10.1016/s0003-4509(04)94297-6.

Abstract

Chronic hyperglycemia in diabetes mellitus is an oxidative stress created by an imbalance of prooxidants over antioxidant defenses. The pathogenesis would involve several mechanisms including glucose autoxidation, protein glycation, the polyol pathway, and overproduction of superoxide radicals in mitochondria and via NAD(P)H oxidase. Glycemic equilibrium plays a very important role in the prooxidant/antioxidant balance. Macromolecules such as found in the extracellular matrix, lipoproteins, and deoxyribonucleic acid also constitute targets for free radicals in diabetes mellitus. This oxidative tress is involved in the pathophysiology of diabetes complications. The chronic hyperglycemic status also favors glycation reactions (irreversible glucose binding on protein amino groups), thereby leading to advanced glycation endproducts. Via their recognition by cell receptors, advanced glycation endproducts also participate in the development of oxidative stress and the inflammatory status. Involvement of oxidative stress and advanced glycation endproducts in diabetes complications is the basis of the development of adjunct therapies with antioxidant and/or anti)advanced glycation endproducts molecules.

摘要

糖尿病中的慢性高血糖是由促氧化剂超过抗氧化防御的失衡所产生的氧化应激。其发病机制涉及多种机制,包括葡萄糖自氧化、蛋白质糖基化、多元醇途径以及线粒体中通过NAD(P)H氧化酶产生超氧自由基。血糖平衡在促氧化剂/抗氧化剂平衡中起着非常重要的作用。细胞外基质、脂蛋白和脱氧核糖核酸等大分子也是糖尿病中自由基的作用靶点。这种氧化应激参与了糖尿病并发症的病理生理过程。慢性高血糖状态也有利于糖基化反应(葡萄糖不可逆地结合在蛋白质氨基上),从而导致晚期糖基化终产物的形成。通过细胞受体对晚期糖基化终产物的识别,它们也参与了氧化应激和炎症状态的发展。氧化应激和晚期糖基化终产物参与糖尿病并发症是开发抗氧化剂和/或抗晚期糖基化终产物分子辅助治疗的基础。

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