晚期糖基化终产物在糖尿病血管并发症中的作用机制

Mechanism of action advanced glycation end products contribute to the development of diabetic vascular complications

晚期糖基化终产物(AGEs)是蛋白质或脂质经过糖基化反应的产物。AGEs存在于糖尿病患者的血管中,促进动脉粥样硬化的发展。多种不同的细胞上AGEs的存在和聚集影响着细胞内外的结构和功能。AGEs通过与细胞外基质基底膜上的分子形成交联和与其受体(RAGE)结合引起多种微血管和大血管并发症。RAGE被AGEs激活后导致转录因子NF-κB和它的靶因子的表达。AGEs可诱发糜蛋白酶的表达和糜蛋白酶依赖性血管紧张素Ⅱ的生成,从而作用于糖尿病血管并发症的发展。

Advanced glycation end products （AGEs） are proteins or lipids that become glycated after exposure to sugars. AGEs are prevalent in the diabetic vasculature and contribute to the development of atherosclerosis. The presence and accumulation of AGEs in many different cell types affect extracellular and intracellular structure and function. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products （RAGE）. Activation of RAGE by AGEs causes upregulation of the transcription factor nuclear factor-κB（NF-κB） and its target genes. AGEs can induce chymase expression and chymase-dependent angiotensin Ⅱ generation,and contribute to the development of diabetic vascular complications.