Zhang Jie, Gao Jie, Guo Guojun, Li Shan, Zhan Gaofeng, Xie Zhongcong, Yang Chun, Luo Ailin
Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
Am J Transl Res. 2018 Aug 15;10(8):2435-2444. eCollection 2018.
Anesthesia and surgery (A + S) are risk factors for patients to develop postoperative delirium (POD). However, the pathogenesis of POD remains largely to be determined. We employed battery of behavioral tests including open-filed test (OFT), elevated plus maze test (EPMT) and buried food test (BFT) to investigate the role of oxidative stress in the development of POD and to explore the therapeutic target for POD in mice after A + S (simple laparotomy under 1.4% isoflurane anesthesia). We initially found that 6 hours after A + S, mice failed to alter the behavioral changes in OFT and the adenosine triphosphate (ATP) level in hippocampus. After hierarchical cluster analysis, however, there was a significant change in the behavior tests between POD unsusceptible (non-POD) and susceptible (POD-like) mice. Interestingly, cyclosporine A, an inhibitor of mitochondrial permeability transition pore (mPTP) opening, exerted pharmacologically beneficial effects on symptoms, decreased reactive oxygen species (ROS) and ATP, and increased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) levels in the hippocampus of POD-like mice. These findings suggest that abnormally activated oxidative stress might be involved in the underlying mechanisms of POD. Novel therapeutic agents targeting inhibition of oxidative stress would provide an available strategy for POD treatment.
麻醉和手术（A + S）是患者发生术后谵妄（POD）的危险因素。然而，POD的发病机制在很大程度上仍有待确定。我们采用了一系列行为测试，包括旷场试验（OFT）、高架十字迷宫试验（EPMT）和埋藏食物试验（BFT），以研究氧化应激在POD发生中的作用，并探索A + S（1.4%异氟烷麻醉下的简单剖腹手术）后小鼠POD的治疗靶点。我们最初发现，A + S后6小时，小鼠在旷场试验中的行为变化以及海马体中的三磷酸腺苷（ATP）水平均未改变。然而，经过层次聚类分析，POD不易感（非POD）和易感（类POD）小鼠在行为测试中存在显著变化。有趣的是，线粒体通透性转换孔（mPTP）开放抑制剂环孢素A对症状产生了药理学上的有益作用，降低了活性氧（ROS）和ATP水平，并提高了类POD小鼠海马体中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）和过氧化氢酶（CAT）的水平。这些发现表明，异常激活的氧化应激可能参与了POD的潜在机制。针对抑制氧化应激的新型治疗药物将为POD治疗提供一种可行的策略。
