Miyata T, Izuhara Y, Sakai H, Kurokawa K
Institute of Medical Sciences and Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Perit Dial Int. 1999;19 Suppl 2:S58-61.
Advanced glycation end-products (AGEs) are formed during non enzymatic glycation and oxidation (glycoxidation) reactions. This process is accelerated in diabetics owing to hyperglycemia, and it has been implicated in the pathogenesis of diabetic complications. Surprisingly, AGEs increase in normoglycemic uremic patients to a much greater extent than in diabetics. AGE accumulation in uremia cannot be attributed to hyperglycemia nor simply to a decreased removal by glomerular filtration. Recently gathered evidence has suggested that, in uremia, the increased carbonyl compounds derived from carbohydrates and lipids modify proteins not only by glycoxidation reaction but also by lipoxidation reaction ("carbonyl stress"). Carbonyl stress has been implicated in the pathogenesis of long-term uremic complications such as dialysis-related amyloidosis. With regard to continuous ambulatory peritoneal dialysis (CAPD), the peritoneal cavity appears to be in a state of severe overload of carbonyl compounds derived from CAPD solution containing high glucose, from heat sterilization of the solution, and from uremic circulation. Carbonyl stress might modify not only peritoneal matrix proteins and alter their structures, but also react with mesothelial and endothelial cell surface proteins and initiate a range of inflammatory responses. Carbonyl stress might therefore contribute to the development of peritoneal sclerosis in patients with long-term CAPD.
晚期糖基化终末产物（AGEs）在非酶糖基化和氧化（糖氧化）反应过程中形成。由于高血糖，这一过程在糖尿病患者中加速，并且它与糖尿病并发症的发病机制有关。令人惊讶的是，血糖正常的尿毒症患者体内AGEs的增加程度比糖尿病患者大得多。尿毒症中AGEs的积累不能归因于高血糖，也不能简单地归因于肾小球滤过清除率的降低。最近收集的证据表明，在尿毒症中，源自碳水化合物和脂质的羰基化合物增加，不仅通过糖氧化反应，而且通过脂氧化反应（“羰基应激”）修饰蛋白质。羰基应激与诸如透析相关淀粉样变等长期尿毒症并发症的发病机制有关。关于持续性非卧床腹膜透析（CAPD），腹膜腔似乎处于一种严重的羰基化合物过载状态，这些羰基化合物来源于含高糖的CAPD溶液、溶液的热灭菌以及尿毒症循环。羰基应激不仅可能修饰腹膜基质蛋白并改变其结构，还可能与间皮细胞和内皮细胞表面蛋白发生反应并引发一系列炎症反应。因此，羰基应激可能导致长期进行CAPD的患者发生腹膜硬化。
