Williamson J R, Chang K, Frangos M, Hasan K S, Ido Y, Kawamura T, Nyengaard J R, van den Enden M, Kilo C, Tilton R G
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri.
Diabetes. 1993 Jun;42(6):801-13. doi: 10.2337/diab.42.6.801.
Vasodilation and increased blood flow are characteristic early vascular responses to acute hyperglycemia and tissue hypoxia. In hypoxic tissues these vascular changes are linked to metabolic imbalances associated with impaired oxidation of NADH to NAD+ and the resulting increased ratio of NADH/NAD+. In hyperglycemic tissues these vascular changes also are linked to an increased ratio of NADH/NAD+, in this case because of an increased rate of reduction of NAD+ to NADH. Several lines of evidence support the likelihood that the increased cytosolic ratio of free NADH/NAD+ caused by hyperglycemia, referred to as pseudohypoxia because tissue partial pressure oxygen is normal, is a characteristic feature of poorly controlled diabetes that mimics the effects of true hypoxia on vascular and neural function and plays an important role in the pathogenesis of diabetic complications. These effects of hypoxia and hyperglycemia-induced pseudohypoxia on vascular and neural function are mediated by a branching cascade of imbalances in lipid metabolism, increased production of superoxide anion, and possibly increased nitric oxide formation.
血管舒张和血流增加是急性高血糖和组织缺氧早期典型的血管反应。在缺氧组织中，这些血管变化与代谢失衡有关，这种失衡与NADH氧化为NAD+受损以及由此导致的NADH/NAD+比值增加有关。在高血糖组织中，这些血管变化也与NADH/NAD+比值增加有关，在这种情况下是由于NAD+还原为NADH的速率增加。几条证据支持这样一种可能性，即高血糖导致的胞质游离NADH/NAD+比值增加，由于组织氧分压正常而被称为假性缺氧，是控制不佳的糖尿病的一个特征，它模拟了真正缺氧对血管和神经功能的影响，并在糖尿病并发症的发病机制中起重要作用。缺氧和高血糖诱导的假性缺氧对血管和神经功能的这些影响是由脂质代谢失衡、超氧阴离子产生增加以及可能增加的一氧化氮形成的分支级联介导的。
