Davì G, Ciabattoni G, Consoli A, Mezzetti A, Falco A, Santarone S, Pennese E, Vitacolonna E, Bucciarelli T, Costantini F, Capani F, Patrono C
Departments of Medicine and Aging, University of Chieti "G. D'Annunzio" School of Medicine, Catholic University School of Medicine,Rome, Italy.
Circulation. 1999 Jan 19;99(2):224-9. doi: 10.1161/01.cir.99.2.224.
Diabetes mellitus (DM) is associated with enhanced lipid peroxidation and persistent platelet activation. We tested the hypothesis that the in vivo formation of the F2-isoprostane 8-iso-prostaglandin (PG)F2alpha, a bioactive product of arachidonic acid peroxidation, is enhanced in DM and contributes to platelet activation.
Urine samples were obtained from 85 diabetic patients and 85 age- and sex-matched healthy subjects for measurement of immunoreactive 8-iso-PGF2alpha and 11-dehydro-thromboxane B2 (TXM), an in vivo index of platelet activation. Sixty-two had non-insulin-dependent (NID)DM, and 23 had insulin-dependent (ID) DM. Vitamin E supplementation, metabolic control, and cyclooxygenase inhibitors were used to investigate the mechanisms of formation of 8-iso-PGF2alpha in this setting. Urinary 8-iso-PGF2alpha excretion was significantly higher (P=0.0001) in NIDDM patients (419+/-208 pg/mg creatinine; range 160 to 1014) than in age-matched control subjects (208+/-92; 41 to 433). Urinary 8-iso-PGF2alpha was linearly correlated with blood glucose and urinary TXM. 8-iso-PGF2alpha excretion was also significantly (P=0. 0001) higher in IDDM patients (400+/-146; 183 to 702) than in control subjects (197+/-69; 95 to 353). Vitamin E supplementation (600 mg/d for 14 days) was associated with a statistically significant reduction in both urinary 8-iso-PGF2alpha (by 37%) and TXM (by 43%) in 10 NIDDM patients. Improved metabolic control was associated with a significant (P=0.0001) reduction in 8-iso-PGF2alpha and TXM excretion by 32% and 41%, respectively, in 21 NIDDM patients. 8-iso-PGF2alpha was unchanged after 2-week dosing with aspirin and indobufen despite profound suppression of TXM excretion.
We conclude that DM is associated with increased formation of F2-isoprostanes, as a correlate of impaired glycemic control and enhanced lipid peroxidation. This may provide an important biochemical link between impaired glycemic control and persistent platelet activation. These results provide a rationale for dose-finding studies of antioxidant treatment in diabetes.
糖尿病（DM）与脂质过氧化增强和血小板持续活化有关。我们检验了以下假设：F2 -异前列腺素8 -异前列腺素（PG）F2α（花生四烯酸过氧化的生物活性产物）在糖尿病患者体内的形成增加，并导致血小板活化。
收集了85例糖尿病患者及85例年龄和性别匹配的健康受试者的尿液样本，用于检测免疫反应性8 -异PGF2α和11 -脱氢血栓素B2（TXM，血小板活化的体内指标）。其中62例为非胰岛素依赖型（NID）糖尿病患者，23例为胰岛素依赖型（ID）糖尿病患者。使用维生素E补充剂、代谢控制和环氧化酶抑制剂来研究在此情况下8 -异PGF2α的形成机制。NIDDM患者尿中8 -异PGF2α排泄量显著高于年龄匹配的对照组（P = 0.0001）（419±208 pg/mg肌酐；范围160至1014），对照组为（208±92；41至433）。尿8 -异PGF2α与血糖及尿TXM呈线性相关。IDDM患者尿8 -异PGF2α排泄量也显著高于对照组（P = 0.0001）（400±146；183至702），对照组为（197±69；95至353）。10例NIDDM患者补充维生素E（600 mg/d，共14天）后，尿8 -异PGF2α（降低37%）和TXM（降低43%）均有统计学显著下降。21例NIDDM患者代谢控制改善后，8 -异PGF2α和TXM排泄量分别显著下降32%和41%（P = 0.0001）。尽管TXM排泄量被显著抑制，但给予阿司匹林和吲哚布芬2周后8 -异PGF2α无变化。
我们得出结论，糖尿病与F2 -异前列腺素形成增加有关，这与血糖控制受损和脂质过氧化增强相关。这可能在血糖控制受损和血小板持续活化之间提供了一个重要的生化联系。这些结果为糖尿病抗氧化治疗的剂量探索研究提供了理论依据。
