AMINOGUANIDINE PREVENTS DIABETES-INDUCED ARTERIAL-WALL PROTEIN CROSS-LINKING
AMINOGUANIDINE PREVENTS DIABETES-INDUCED ARTERIAL-WALL PROTEIN CROSS-LINKING
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DOI：
10.1126/science.3487117
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发表时间：
1986-06-27
期刊：
影响因子：
56.9
通讯作者：
CERAMI, A
中科院分区：
文献类型：
--
作者：
BROWNLEE, M;VLASSARA, H;CERAMI, A
糖尿病会加速胶原蛋白交联的年龄相关性增加以及晚期糖基化产物的积累，这表明葡萄糖衍生的交联形成可能导致慢性糖尿病并发症的发展以及衰老的某些生理变化。氨基胍是一种亲核肼化合物，在体外既能阻止荧光性晚期非酶糖基化产物的形成，也能阻止葡萄糖衍生的胶原蛋白交联的形成。给大鼠施用氨基胍在体内同样能有效防止糖尿病诱导的荧光性晚期非酶糖基化产物的形成以及动脉壁结缔组织蛋白的交联。氨基胍作为晚期非酶糖基化产物形成抑制剂的发现，现在使得对这一过程的致病意义进行精确的实验界定成为可能，并提示氨基胍在未来慢性糖尿病并发症治疗中具有潜在的临床作用。
Age-associated increases in collagen cross-linking and accumulation of advanced glycosylation products are both accelerated by diabetes, suggesting that glucose-derived cross-link formation may contribute to the development of chronic diabetic complications as well as certain physical changes of aging. Aminoguanidine, a nucleophilic hydrazine compound, prevented both the formation of fluorescent advanced nonenzymatic glycosylation products and the formation of glucose-derived collagen cross-links in vitro. Aminoguanidine administration to rats was equally effective in preventing diabetes-induced formation of fluorescent advanced nonenzymatic glycosylation products and cross-linking of arterial wall connective tissue protein in vivo. The identification of aminoguanidine as an inhibitor of advanced nonenzymatic glycosylation product formation now makes possible precise experimental definition of the pathogenetic significance of this process and suggests a potential clinical role for aminoguanidine in the future treatment of chronic diabetic complications.