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产后女性童年期受虐经历与脂质过氧化及DNA损伤的关联

The Association of Childhood Maltreatment With Lipid Peroxidation and DNA Damage in Postpartum Women.

作者信息

Boeck Christina, Gumpp Anja M, Koenig Alexandra M, Radermacher Peter, Karabatsiakis Alexander, Kolassa Iris-Tatjana

机构信息

Clinical and Biological Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany.

Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital Ulm, Ulm, Germany.

出版信息

Front Psychiatry. 2019 Feb 18;10:23. doi: 10.3389/fpsyt.2019.00023. eCollection 2019.

DOI:10.3389/fpsyt.2019.00023
PMID:30833908
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6387959/
Abstract

Childhood maltreatment (CM) is associated with an increased risk for the development of psychiatric and somatic disorders in later life. A potential link could be oxidative stress, which is defined as the imbalance between the amount of reactive oxygen species (ROS) and the neutralizing capacity of anti-oxidative defense systems. However, the findings linking CM with oxidative stress have been inconsistent so far. In this study, we aimed to further explore this association by investigating biological markers of DNA and lipid damage due to oxidation in a comprehensive approach over two study cohorts of postpartum women (study cohort I and study cohort II). The severity of CM experiences (maltreatment load) was assessed in both studies using the . In study cohort I ( = 30), we investigated whether CM was associated with higher levels of structural DNA damage in peripheral blood mononuclear cells (PBMC) by two methods that are highly sensitive for detecting nuclear DNA strand breaks (comet assay and γH2AX staining). In study cohort II ( = 117), we then assessed in a larger cohort, that was specifically controlled for potential confounders for oxidative stress measurements, two established serum and plasma biomarkers of oxidative stress, one representing oxidative DNA and RNA damage (8-hydroxy-2'-deoxyguanosine and 8-hydroxyguanosine; 8-OH(d)G) and the other representing lipid peroxidation (8-isoprostane). In study cohort I, the analyses revealed no significant main effects of maltreatment load on cellular measures of nuclear DNA damage. The analyses of peripheral oxidative stress biomarkers in study cohort II revealed a significant main effect of maltreatment load on free 8-isoprostane plasma levels, but not on total 8-isprostane plasma levels and 8-OH(d)G serum levels. Taken together, by combining different methods and two study cohorts, we found no indications for higher oxidative DNA damages with higher maltreatment load in postpartum women. Further research is needed to investigate whether this increase in free 8-isoprostane is a marker for oxidative stress or whether it is instead functionally involved in ROS-related signaling pathways that potentially regulate inflammatory processes following a history of CM.

摘要

童年期虐待(CM)与日后患精神疾病和躯体疾病的风险增加有关。一个潜在的联系可能是氧化应激,它被定义为活性氧(ROS)的量与抗氧化防御系统的中和能力之间的失衡。然而,迄今为止,将CM与氧化应激联系起来的研究结果并不一致。在本研究中,我们旨在通过对两个产后女性研究队列(研究队列I和研究队列II)采用综合方法调查氧化导致的DNA和脂质损伤的生物标志物,进一步探索这种关联。在两项研究中均使用[具体量表名称未给出]评估CM经历的严重程度(虐待负荷)。在研究队列I(n = 30)中,我们通过两种对检测核DNA链断裂高度敏感的方法(彗星试验和γH2AX染色)研究CM是否与外周血单核细胞(PBMC)中更高水平的结构性DNA损伤相关。在研究队列II(n = 117)中,我们随后在一个更大的队列中进行评估,该队列专门针对氧化应激测量的潜在混杂因素进行了控制,评估了两种已确立的氧化应激血清和血浆生物标志物,一种代表氧化的DNA和RNA损伤(8 - 羟基 - 2'-脱氧鸟苷和8 - 羟基鸟苷;8 - OH(d)G),另一种代表脂质过氧化(8 - 异前列腺素)。在研究队列I中,分析显示虐待负荷对核DNA损伤的细胞测量指标没有显著的主效应。研究队列II中外周氧化应激生物标志物的分析显示,虐待负荷对游离8 - 异前列腺素血浆水平有显著的主效应,但对总8 - 异前列腺素血浆水平和8 - OH(d)G血清水平没有影响。综上所述,通过结合不同方法和两个研究队列,我们发现没有迹象表明产后女性中虐待负荷越高,氧化DNA损伤就越高。需要进一步研究来调查游离8 - 异前列腺素的这种增加是氧化应激的标志物,还是相反,它在潜在调节CM病史后炎症过程的ROS相关信号通路中发挥功能作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f22/6387959/4c8ee06bd6f0/fpsyt-10-00023-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f22/6387959/4c8ee06bd6f0/fpsyt-10-00023-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f22/6387959/4c8ee06bd6f0/fpsyt-10-00023-g0001.jpg

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