Role of oxidative DNA damage in the pathogenesis of diabetic complications

由高血糖引起的氧化应激增强可能参与糖尿病并发症的发病机制。氧化应激可促进脱氧鸟苷（dG）向8-氧代，2 ′-脱氧鸟苷（8-oxodG）的转化。为探讨DNA氧化损伤在糖尿病并发症发生中的作用，我们测定了2型糖尿病患者尿和血单个核细胞中8-oxodG含量，结果表明，2型糖尿病患者尿和血单个核细胞中8-oxodG含量均明显高于对照组。尿中8-oxodG排泄量与单核细胞中8-oxodG含量显著相关（R=0.855，p<0.0001）。尿中8-oxodG含量（R=0.783，p<0.0001）和单核细胞中8-oxodG含量（R=0.796，p<0.0001）均高于正常对照组（P <0.05）。<0.0001）与血红蛋白A1 c水平相关。尿8-oxodG排泄和单核细胞中8-oxodG含量与糖尿病肾病和视网膜病变的严重程度成比例增加。这些数据提供了证据表明，糖尿病中增加的氧化DNA损伤与糖尿病并发症有关。这是第一份报告显示，8-oxodG的增加与糖尿病并发症的严重程度成正比。氧化性DNA损伤被认为是糖尿病并发症的发病机制之一。8-尿和单核细胞中的oxodG是评估糖尿病患者中氧化DNA损伤的有用标志物。

Augmented oxidative stress induced by hyperglycemia may contribute to the pathogenesis of diabetic complications. Oxidative stress is known to increase the conversion of deoxyguanosine(dG) to 8-oxo, 2'-deoxyguanosine (8-oxodG) in DNA.To investigate the possible. contribution of oxidative DNA damage to the pathogenesis of diabetic complicfttions, we measured the 8-oxodGcontents in the urine and the blood mononuclear cells of type 2 diabetic patients.The contents of 8-oxodG in the urine and the mononuclear cells of the type 2 diabetic patients were much higher than those of the control subjects. Urinary excretion of 8-oxodG was significantly correlated with the 8-oxodG content in the mononuclear cells (R=0.855, p<0.0001). The 8-oxodGcontents in the urine (R=0.783, p<0.0001) and mononuclear cells (R=0.796, p.<0.0001) were correlated with the hemoglobin A1c level. Urinary 8-oxodG excretion and the 8-oxodG content in the mononuclear cells were augmented in proportion to the severity of diabetic nephropathy as well as retinopathy. These data provide evidence that augmented oxidative DNA damage in diabetes is linked to diabetic complications.This is the first report showing that the increase in 8-oxodG is proportional to the severity of diabetic complications. Oxidative DNA damage is speculated to contribute to the pathogenesis of diabetic complications. 8-oxodG in urine and mononuclear cells is a useful marker to evaluate oxidative DNA damage in diabetic patients.