Goligorsky M S, Chen J, Brodsky S
Departments of Medicine, Physiology, and Biophysics, and the Program on Biomedical Engineering, State University of New York, Stony Brook, USA.
Hypertension. 2001 Feb;37(2 Pt 2):744-8. doi: 10.1161/01.hyp.37.2.744.
Clinical manifestations of diabetic nephropathy are an expression of diabetic microangiopathy. This review revisits the previously proposed Steno hypothesis and advances our hypothesis that development of endothelial cell dysfunction represents a common pathophysiological pathway of diabetic complications. Specifically, the ability of glucose to scavenge nitric oxide is proposed as the initiation phase of endothelial dysfunction. Gradual accumulation of advanced glycated end products and induction of plasminogen activator inhibitor-1, resulting in the decreased expression of endothelial nitric oxide synthase and reduced generation of nitric oxide, are proposed to be pathophysiologically critical for the maintenance phase of endothelial dysfunction. The proposed conceptual shift toward the role of endothelial dysfunction in diabetic complications may provide new strategies for their prevention.
糖尿病肾病的临床表现是糖尿病微血管病变的一种表现。本综述重新审视了先前提出的斯滕诺假说，并提出了我们的假说，即内皮细胞功能障碍的发生代表了糖尿病并发症的共同病理生理途径。具体而言，葡萄糖清除一氧化氮的能力被认为是内皮功能障碍的起始阶段。晚期糖基化终末产物的逐渐积累和纤溶酶原激活物抑制剂-1的诱导，导致内皮型一氧化氮合酶表达降低和一氧化氮生成减少，被认为在病理生理上对内皮功能障碍的维持阶段至关重要。所提出的关于内皮功能障碍在糖尿病并发症中作用的概念转变可能为其预防提供新策略。
