Coughlan Melinda T, Cooper Mark E, Forbes Josephine M
Danielle Alberti Memorial Centre for Diabetes Complications, Baker Heart Research Institute, P.O. Box 6492, St. Kilda Rd. Central, Melbourne 8008, Australia.
Ann N Y Acad Sci. 2005 Jun;1043:750-8. doi: 10.1196/annals.1333.087.
Although advanced glycation end products (AGEs) have been postulated to contribute to diabetic nephropathy in their own right, advanced glycation is clearly only one pathway by which renal injury may be induced in diabetes. The interaction between metabolic and hemodynamic factors amplifies the deleterious effects of the diabetic milieu, thereby reducing the threshold for microvascular injury via common mechanisms. This includes interactions between AGE-mediated pathways and the renin angiotensin system, oxidative stress, protein kinase C, and growth factors, which play a significant role in the development and progression of diabetic renal disease. As it is likely that the future of preventive therapy will not involve a single "cure-all" agent, it seems that a highly relevant question in diabetic nephropathy should be, which pathogenic pathways are already addressed by currently available therapies? Combination therapies that target multiple pathways may ultimately be more successful than those that modify a single pathway. Therefore, research into synergistic interactions among the various pathogenic pathways leading to diabetic complications is critical in order to develop interventions that confer optimal end-organ protection.
尽管晚期糖基化终末产物（AGEs）被认为自身会导致糖尿病肾病，但晚期糖基化显然只是糖尿病中可能诱发肾损伤的一条途径。代谢和血流动力学因素之间的相互作用会放大糖尿病环境的有害影响，从而通过共同机制降低微血管损伤的阈值。这包括AGE介导的途径与肾素血管紧张素系统、氧化应激、蛋白激酶C和生长因子之间的相互作用，它们在糖尿病肾病的发生和发展中起重要作用。由于未来的预防性治疗可能不会涉及单一的“万灵药”，糖尿病肾病中一个高度相关的问题似乎应该是，目前可用的治疗方法已经针对了哪些致病途径？针对多种途径的联合治疗可能最终比那些只改变单一途径的治疗更成功。因此，研究导致糖尿病并发症的各种致病途径之间的协同相互作用对于开发能提供最佳终末器官保护的干预措施至关重要。
