VASCULAR IRON DEPOSITION & DIABETIC COMPLICATIONS

患有糖尿病的人和动物发育周围神经和 血管功能障碍。有趣的是，早期的神经血流量和 糖尿病动物的神经传导缺陷可通过以下方法完全纠正 铁络合剂的给药，如去铁胺和 曲安替丁。作为一种潜在的解释，这相当令人惊讶 铁络合剂的作用，我们假设以下顺序 事件(I)糖分升高导致蛋白质糖基化增强， 尤其是长寿蛋白质，如弹性蛋白和胶原蛋白 是内部弹性层的主要组成部分。(Ii) 弹性蛋白和胶原蛋白的糖基化产生结合铁的结构 在体内导致了一种铁质屏障的形成 就在血管内皮下。(Iii)这是富含铁的 亚内皮细胞蛋白基质将通过铁介导的过程 -催化破坏内皮细胞衍生的松弛因子一氧化氮 氧化物。(Iv)由此导致的内皮依赖性血管环缺陷 乳酸氧化导致血管收缩，慢性外周缺血， 最后，周围神经功能障碍和死亡。这个 我们的ESR实验工作的目标是：(I)尝试 测定糖化蛋白质的性质：铁加合物(S)，(Ii) 检查这些加合物与一氧化氮相互作用的程度 以及，如有可能，(三)确定硝酸盐的寿命 氧化物：铁：糖化蛋白质复合体。

Humans and animals with diabetes develop peripheral nerve and vascular dysfunction. Interestingly, the early nerve blood flow and nerve conduction deficits in diabetic animals are fully corrected by administration of iron chelators such as desferrioxamine and trientine. As a potential explanation for this rather surprising effect of iron chelators, we hypothesize the following sequence of events (i) Elevated sugars lead to enhanced protein glycation, particularly in long-lived proteins such as elastin and collagen which are major constituents of the internal elastic laminae. (ii) Glycation of elastin and collagen produces structures which bind iron leading, in vivo, to the formation of a ferruginous barrier immediately beneath the endothelium. (iii) This iron-rich sub-endothelial protein matrix will - through iron-mediated processes - catalytically destroy endothelium-derived relaxing factor nitric oxide. (iv) The resultant defect in endothelium-dependent vascular r ela xation leads to vasoconstriction, chronic peripheral ischemia, and, finally, dysfunction and death of peripheral nerves. The objective of our experimental work with ESR are: (i) Attempt to determine the nature of the glycated protein:iron adducts(s), (ii) examine the extent to which these adducts interact with nitric oxide and, if possible, (iii) determine the life-span of the nitric oxide:iron:glycated protein complexes.