1 型和 2 型糖尿病氧化应激、DNA 损伤和 DNA 修复的参数。

Parameters of oxidative stress, DNA damage and DNA repair in type 1 and type 2 diabetes mellitus.

机构信息

Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno.

出版信息

Arch Physiol Biochem. 2011 Oct;117(4):222-30. doi: 10.3109/13813455.2010.551135. Epub 2011 Feb 22.

DOI:10.3109/13813455.2010.551135

PMID:21338322

Abstract

OBJECTIVES

(i) to determine the extent of oxidative stress and DNA damage and repair using a panel of selected markers in patients with type 1 and type 2 diabetes mellitus (T1DM, T2DM), (ii) to find their possible relationships with diabetes compensation and duration, and finally (iii) to test for the effect of functional polymorphisms in the 8-oxoguanin DNA glycosylase (rs1052133), catalase (rs1001179) and superoxide dismutase (rs4880) genes on respective intermediate phenotypes.

METHODS

A total of 207 subjects (23 children and 44 adults with T1DM, 52 adult patients with T2DM and 88 healthy adult control subjects) were enrolled in the study. The following markers of redox state were determined in participants: erythrocyte superoxide dismutase (Ery-SOD), whole blood glutathione peroxidase (WB-GPx), erythrocyte glutathione (Ery-GSH), plasma total antioxidant capacity (P-tAOC) and plasma malondialdehyde (P-MDA). Furthermore, the extent of DNA damage and repair was ascertained using the following parameters: DNA single strand breaks (DNAssb), DNA repair capacity (DNArc) and DNA repair index (DNRI).

RESULTS

Comparison of T1DM vs. T2DM patients revealed significantly higher Ery-GSH content (P < 0.0001) and significantly lower Ery-SOD activity (P = 0.0006) and P-tAOC level (P < 0.0001) in T1DM subjects. T2DM diabetics exhibited a significant increase in DNAssb (P < 0.0001) and significant decrease in both DNArc (P < 0.0001) and DNRI (P < .0001) compared with T1DM patients. Patient's age (irrespective of DM type) significantly correlated with DNAssb (r = 0.48, P < 0.0001), DNArc (r = -0.67, P < 0.0001) and DNRI (r = -0.7, P < 0.0001). Allele frequencies of all studied polymorphisms did not exhibit any significant association with the investigated parameters.

CONCLUSION

We demonstrated significant age- and DM type-related changes of oxidative DNA modification and capacity for its repair in subjects with T1DM and T2DM.

摘要

目的

（i）使用选定标记物的面板确定 1 型和 2 型糖尿病（T1DM、T2DM）患者的氧化应激和 DNA 损伤及修复程度，（ii）研究其与糖尿病代偿和持续时间的可能关系，最后（iii）测试 8-氧鸟嘌呤 DNA 糖基化酶（rs1052133）、过氧化氢酶（rs1001179）和超氧化物歧化酶（rs4880）基因的功能多态性对各自中间表型的影响。

方法

共纳入 207 名受试者（23 名儿童和 44 名 T1DM 成人、52 名 T2DM 成年患者和 88 名健康成年对照组）。参与者的氧化还原状态的以下标记物：红细胞超氧化物歧化酶（Ery-SOD）、全血谷胱甘肽过氧化物酶（WB-GPx）、红细胞谷胱甘肽（Ery-GSH）、血浆总抗氧化能力（P-tAOC）和血浆丙二醛（P-MDA）。此外，通过以下参数确定 DNA 损伤和修复的程度：DNA 单链断裂（DNAssb）、DNA 修复能力（DNArc）和 DNA 修复指数（DNRI）。

结果

T1DM 与 T2DM 患者的比较显示，T1DM 患者的 Ery-GSH 含量显著升高（P < 0.0001），Ery-SOD 活性（P = 0.0006）和 P-tAOC 水平（P < 0.0001）显著降低。T2DM 糖尿病患者的 DNAssb 显著增加（P < 0.0001），DNArc（P < 0.0001）和 DNRI（P < 0.0001）显著降低。与 T1DM 患者相比，患者的年龄（无论 DM 类型如何）与 DNAssb（r = 0.48，P < 0.0001）、DNArc（r = -0.67，P < 0.0001）和 DNRI（r = -0.7，P < 0.0001）显著相关。所有研究多态性的等位基因频率与所研究的参数均无显著相关性。