Whiteside Catharine I
Department of Medicine, University of Toronto, 1 King's College Circle, Room 2113, Toronto, ON M5S 1A8, Canada.
Curr Hypertens Rep. 2005 Apr;7(2):148-54. doi: 10.1007/s11906-005-0090-4.
High glucose activates a myriad of signaling and gene expression pathways in non-insulin-dependent target cells causing diabetes complications. One of the earliest responses to high glucose by vascular cells is the generation of reactive oxygen species (ROS) that act directly on intracellular proteins and DNA, or indirectly as second messengers, transforming these cells into disease phenotypes. ROS are produced by mitochondria and/or NADPH oxidase in all target cells exposed to high glucose studied to date. Reports using cell cultures and diabetic animal models indicate that inhibition of ROS generation prevents the amplification of signaling and gene expression that are implicated in vascular complications. These models convincingly demonstrate that maneuvers preventing ROS production attenuate or completely abrogate early micro- and macrovascular end-organ damage of diabetes, including nephropathy, retinopathy, and large-vessel atherosclerosis. Attention now turns to the development of more effective antioxidants that could be used in clinical trials in the prevention and treatment of diabetes complications.
高血糖会激活非胰岛素依赖型靶细胞中的众多信号传导和基因表达途径，从而引发糖尿病并发症。血管细胞对高血糖的最早反应之一是产生活性氧（ROS），ROS可直接作用于细胞内蛋白质和DNA，或间接作为第二信使，将这些细胞转变为疾病表型。在迄今为止研究的所有暴露于高血糖的靶细胞中，线粒体和/或NADPH氧化酶都会产生活性氧。使用细胞培养和糖尿病动物模型的报告表明，抑制活性氧的产生可防止与血管并发症相关的信号传导和基因表达的放大。这些模型令人信服地证明，阻止活性氧产生的措施可减轻或完全消除糖尿病早期微血管和大血管终末器官损伤，包括肾病、视网膜病变和大血管动脉粥样硬化。现在人们的注意力转向开发更有效的抗氧化剂，可用于预防和治疗糖尿病并发症的临床试验。
