摘要
在全球范围内,糖尿病及其并发症已成为危害人类健康的最重要的疾病之一,糖尿病肾病已成为导致终末期肾功能不全的首要原因,严重影响了人类的生活质量和寿命。尽管临床研究已经证实,血糖升高是糖尿病各种并发症发生的重要危险因素,但有效地控制血糖并不能完全阻止糖尿病各种并发症的发生和发展。近年来氧化应激在糖尿病及其并发症发生和发展中的作用日益受到人们的重视。在与高血糖有关的多个生化过程中均伴随着活性氧的生成,包括葡萄糖自氧化,多元醇途径,前列腺素类的合成,蛋白质的糖基化等等。葡萄糖在自氧化过程中不产生分子氧,而是产生氧化反应的中间产物,包括超氧阴离子(O~(2-)·),羟自由基(·OH)和过氧化氢(H_2O_2)。体内过度产生的活性氧可交联脂质、蛋白质等大分子活性物质,损伤血管内皮细胞,诱导炎症介质的释放,进一步造成组织和器官的功能受损。晚期蛋白质氧化产物(AOPPs)最早由Witko-Sarsat等在尿毒症患者的血浆中发现。将血浆或纯化的人血清白蛋白在体外与次氯酸混合,产生AOPPs的浓度可随次氯酸浓度增高呈剂量依赖性增加。双酪氨酸为蛋白质被氧化后的结构特征,AOPPs在血浆中的浓度与双酪氨酸和
Diabetes is the leading cause of end-stage renal disease worldwide. Although clinical studies have demonstrated a clear link between hyperglycemia and the development of diabetic complications of diabetes, the mechanisms through which excess glucose results in tissue damage remain incompletely understand. Accumulated evidence indicate that the over generation of reactive oxygen species(ROS) (oxidative stress) may play an important role in the etiology of diabetic complications. This hypothesis is supported by evidence indicating that many biochemical pathways strictly associated with hyperglycemia (glucose autoxidation, polyol pathway, prostanoid synthesis, protein glycation) can increase the production of free radicals. Accumulation of plasma advanced oxidation protein products (AOPPs) has been found firstly in patients with chronic kidney disease (CKD). AOPPs can be formed in vitro by exposure of serum albumin to hypochlorous acid
引文
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