Miyata T, Iida Y, Horie K, Cai Z, Sugiyama S, Maeda K
Department of Internal Medicine, Branch Hospital, Nagoya University School of Medicine, Japan.
Nephrol Dial Transplant. 1996;11 Suppl 5:27-30. doi: 10.1093/ndt/11.supp5.27.
beta 2-Microglobulin is a major constituent of amyloid fibrils in dialysis-related amyloidosis, a serious complication leading to bone and joint destruction in long-term haemodialysis patients. However, the molecular pathogenesis of this complication remains unknown. Intact beta 2-microglobulin per se seems an unlikely contributor to the pathogenesis, because no difference in the plasma levels of intact beta 2-microglobulin has yet been found between haemodialysis patients with and without this complication. Some investigators have therefore focused on the modification of this molecule. Recent studies have revealed a new modification of beta 2-microglobulin in amyloid fibrils-the advanced glycation end-products (AGEs) formed by a non-enzymatic reaction between sugar aldose and protein. Further studies have suggested that the interaction of AGE-modified beta 2-microglobulin with monocyte/macrophage and osteoclast/osteoblast gives a plausible albeit partial explanation for the mechanism of bone and joint destruction in dialysis-related amyloidosis. This article discusses the pathophysiology of AGEs in renal failure and the modification of beta 2-microglobulin with AGEs, especially focusing on their structure and pathological role in dialysis-related amyloidosis.
β2-微球蛋白是透析相关性淀粉样变中淀粉样纤维的主要成分，这是一种严重并发症，可导致长期血液透析患者的骨骼和关节破坏。然而，这种并发症的分子发病机制仍不清楚。完整的β2-微球蛋白本身似乎不太可能是发病机制的促成因素，因为在有或没有这种并发症的血液透析患者之间，尚未发现完整的β2-微球蛋白血浆水平有差异。因此，一些研究人员将重点放在了该分子的修饰上。最近的研究揭示了淀粉样纤维中β2-微球蛋白的一种新修饰——由糖醛糖与蛋白质之间的非酶反应形成的晚期糖基化终产物（AGEs）。进一步的研究表明，AGE修饰的β2-微球蛋白与单核细胞/巨噬细胞以及破骨细胞/成骨细胞之间的相互作用，为透析相关性淀粉样变中骨骼和关节破坏的机制提供了一个合理但不完整的解释。本文讨论了肾衰竭中AGEs的病理生理学以及β2-微球蛋白的AGE修饰，尤其关注它们在透析相关性淀粉样变中的结构和病理作用。
