Hou F F, Chertow G M, Kay J, Boyce J, Lazarus J M, Braatz J A, Owen W F
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Kidney Int. 1997 May;51(5):1514-9. doi: 10.1038/ki.1997.208.
Dialysis related amyloidosis (DRA) is a progressive debilitating complication of long-term dialysis. beta 2-microglobulin (beta 2m) amyloid deposition occurs preferentially in older patients and initially is located in collagen-rich osteo-articular tissues. Since an age-dependent increase in the formation of advanced glycation end products (AGE) has been observed in collagen-containing structures, we hypothesized that AGE-modified beta 2m in the amyloid of DRA may be formed locally in osteo-articular structures as a subsequent event of its binding to collagen-AGE. Based on this hypothesis, we investigated the binding between beta 2m and AGE-modified collagen (collagen-AGE) in vitro. Significantly larger amounts of human beta 2m were bound to types I to IV of immobilized collagen-AGE than to unmodified collagens (P < 0.0001). The quantity of beta 2m bound to collagen-AGE was dependent on the concentrations of both beta 2m and of AGE contained in collagen (P < 0.01). Unmodified beta 2m was more avidly bound to collagen-AGE or collagen in comparison to AGE-modified beta 2m (P < 0.0001). beta 2m bound to collagen-AGE could be modified further by nonenzymatic glycosylation during three weeks of incubation with physiologic concentrations of glucose. Similar processes in vivo may be important in the pathobiology of DRA.
透析相关性淀粉样变（DRA）是长期透析的一种进行性致残并发症。β2微球蛋白（β2m）淀粉样沉积优先发生于老年患者，最初位于富含胶原蛋白的骨-关节组织中。由于在含胶原蛋白的结构中已观察到晚期糖基化终产物（AGE）的形成随年龄增长而增加，我们推测DRA淀粉样变中AGE修饰的β2m可能在骨-关节结构中局部形成，作为其与胶原-AGE结合的后续事件。基于这一假设，我们在体外研究了β2m与AGE修饰的胶原蛋白（胶原-AGE）之间的结合。与未修饰的胶原蛋白相比，固定化胶原-AGE的I型至IV型结合的人β2m量显著更多（P < 0.0001）。与胶原-AGE结合的β2m量取决于β2m和胶原中AGE的浓度（P < 0.01）。与AGE修饰的β2m相比，未修饰的β2m与胶原-AGE或胶原蛋白的结合更紧密（P < 0.0001）。在与生理浓度葡萄糖孵育三周期间，与胶原-AGE结合的β2m可通过非酶糖基化进一步修饰。体内的类似过程在DRA的病理生物学中可能很重要。
