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氧化应激和晚期糖基化终产物的可溶性受体在心脏手术后谵妄的病理生理学中起作用。

Oxidative stress and soluble receptor for advanced glycation end-products play a role in the pathophysiology of delirium after cardiac surgery.

机构信息

Department of Old Age Psychiatry and Psychotic Disorders, Faculty of Gerontology, Medical University of Lodz, Czechoslowacka 8/10, 92-216, Lodz, Poland.

Central Clinical Hospital, Medical University of Lodz, Lodz, Poland.

出版信息

Sci Rep. 2021 Dec 8;11(1):23646. doi: 10.1038/s41598-021-03007-2.

DOI:10.1038/s41598-021-03007-2
PMID:34880331
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8655063/
Abstract

Coronary-artery bypass graft (CABG) surgery is known to improve cardiac function and decrease mortality, albeit, this method of treatment is also associated with a neuropsychiatric complications including postoperative delirium. The pathophysiology of delirium after cardiac surgery remains poorly understood. Thus, the purpose of this study was to investigate whether oxidative stress reflected by decreased preoperative and postoperative plasma antioxidant activity is independently associated with delirium after cardiac surgery. The second aim was to assess whether decreased antioxidant activity is stress-related or mediated by other pathologies such as major depressive disorder (MDD), anxiety disorders, and cognitive impairment. Furthermore, the putative relationship between pre- and postoperative soluble receptor for advanced glycation end-products (sRAGE) overexpression and plasma antioxidant capacity was evaluated. The patients cognitive status was assessed 1 day preoperatively with the use of the Mini-Mental State Examination Test and the Clock Drawing Test. A diagnosis of MDD and anxiety disorders was established on the basis of DSM-5 criteria. Blood samples for antioxidant capacity and sRAGE levels were collected both preoperatively and postoperatively. The Confusion Assessment Method for the Intensive Care Unit was used within the first 5 days postoperatively to screen for a diagnosis of delirium. Postoperative delirium was diagnosed in 34% (61 of 177) of individuals. Multivariate logistic regression analysis revealed that low baseline antioxidant capacity was independently associated with postoperative delirium development. Moreover, increased risk of delirium was observed among patients with a preoperative diagnosis of MDD associated with antioxidant capacity decreased postoperatively. According to receiver operating characteristic analysis, the most optimal cutoff values of the preoperative and postoperative antioxidant capacity that predict the development of delirium were 1.72 mM and 1.89 mM, respectively. Pre- and postoperative antioxidant capacity levels were negatively correlated with postoperative sRAGE concentration (Spearman's Rank Correlation - 0.198 and - 0.158, p < 0.05, respectively). Patients with decreased preoperative antioxidant activity and those with depressive episodes complicated with lower postoperative antioxidant activity are at significantly higher risk of delirium after cardiac surgery development. sRAGE overexpression may be considered as protective mechanism against increased oxidative stress and subsequent cell damage.

摘要

冠状动脉旁路移植术 (CABG) 已被证实可改善心脏功能并降低死亡率,但该治疗方法也与包括术后谵妄在内的神经精神并发症相关。心脏手术后谵妄的病理生理学仍知之甚少。因此,本研究旨在探讨术前和术后血浆抗氧化活性降低是否与心脏手术后谵妄独立相关。研究的第二个目的是评估抗氧化活性降低是否与应激相关,或者是否由其他病理情况(如重度抑郁症、焦虑症和认知障碍)介导。此外,还评估了术前和术后可溶性晚期糖基化终产物受体 (sRAGE) 过表达与血浆抗氧化能力之间的假定关系。患者的认知状态在术前 1 天使用简易精神状态检查测试和时钟绘图测试进行评估。根据 DSM-5 标准确定重度抑郁症和焦虑症的诊断。在术前和术后均采集血液样本用于检测抗氧化能力和 sRAGE 水平。术后第 1 天至第 5 天内使用重症监护病房谵妄评估方法进行筛查,以诊断谵妄。61 例(177 例中的 34%)患者被诊断为术后谵妄。多变量逻辑回归分析显示,基线时抗氧化能力低与术后谵妄的发生独立相关。此外,术前诊断为重度抑郁症并伴有术后抗氧化能力降低的患者发生谵妄的风险增加。根据接收者操作特征分析,预测谵妄发生的最佳术前和术后抗氧化能力截断值分别为 1.72 mM 和 1.89 mM。术前和术后抗氧化能力水平与术后 sRAGE 浓度呈负相关(Spearman 秩相关 -0.198 和 -0.158,p<0.05)。术前抗氧化活性降低的患者和伴有术后抗氧化活性降低的抑郁发作患者发生心脏手术后谵妄的风险显著增加。sRAGE 过表达可能被视为一种针对氧化应激增加和随后细胞损伤的保护机制。

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