Rösen P, Du X, Tschöpe D
Diabetes Research Institute, Heinrich-Heine-University, Düsseldorf, Germany.
Mol Cell Biochem. 1998 Nov;188(1-2):103-11.
The evidence that the generation of reactive oxygen intermediates (ROI) plays an important role for the increased cardiovascular risk in diabetes is summarised. In addition to the well known parameters of oxidative stress as lipid hydroperoxides and thiobarbituric acid substances (TBARS), recent observations indicate that isoprostanes which can be taken as a more specific parameter of oxidative stress, are generated in higher amounts by diabetic patients. This increased formation of isoprostanes can be inhibited by an installment of a close metabolic control or the supplementation with tocopherol. The cause for the elevated oxidative stress is not yet fully understood, however the autoxidation of glucose, the formation of advanced glycation endproducts and the activation of NADPH-oxidase seem to be relevant processes. Since ROI are able to quench nitric oxide and to inhibit the synthesis of prostacyclin, the antithrombotic, vasodilating and antiatherosclerotic properties of endothelium are impaired in diabetes. Additionally, the balance of endothelial mediators released by endothelium is shifted to angiotensin II and endothelin, compounds which enhance the proliferation of smooth muscle cells and may limit the coronary reserve of myocardium. The activation of the transcription factor NF-kappa B by glucose and its autoxidative products is regarded as a key event in the transformation of the vasculature in diabetes. Epidemiological observations and very recent clinical studies underlie the impact of ROI for the development of cardiovascular complications in diabetes and suggest that an antioxidative treatment might be helpful to reduce the cardiac risk in diabetes.
本文总结了活性氧中间体（ROI）的产生在糖尿病患者心血管疾病风险增加中起重要作用的证据。除了氧化应激的常见参数如脂质氢过氧化物和硫代巴比妥酸物质（TBARS）外，最近的观察表明，异前列腺素可作为氧化应激的更特异性参数，糖尿病患者体内产生的异前列腺素量更高。通过实施严格的代谢控制或补充生育酚可以抑制异前列腺素的这种增加形成。氧化应激升高的原因尚未完全明确，然而葡萄糖的自氧化、晚期糖基化终产物的形成以及NADPH氧化酶的激活似乎是相关过程。由于ROI能够消耗一氧化氮并抑制前列环素的合成，糖尿病患者内皮的抗血栓、血管舒张和抗动脉粥样硬化特性受损。此外，内皮释放的内皮介质平衡转向血管紧张素II和内皮素，这些化合物可增强平滑肌细胞的增殖并可能限制心肌的冠状动脉储备。葡萄糖及其自氧化产物对转录因子NF-κB的激活被认为是糖尿病血管病变中的关键事件。流行病学观察和最近的临床研究证实了ROI对糖尿病心血管并发症发生发展的影响，并表明抗氧化治疗可能有助于降低糖尿病患者的心脏风险。
