乌司他丁减轻青春期小鼠重复氯胺酮暴露诱发的认知障碍。

IF 3 4区 医学 Q2 NEUROSCIENCES Neural Plasticity Pub Date : 2022-01-01 DOI:10.1155/2022/6168284
Yu Hong, Shiyu Meng, Shouping Wang, Ting Liu, Jiayi Liu
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引用次数: 1

摘要

氯胺酮(Ketamine, KET)广泛用于麻醉诱导和维持,治疗抑郁症患者需要长期使用。反复使用KET与情绪和记忆障碍有关。乌司他丁(UTI)是一种尿胰蛋白酶抑制剂,已被广泛用作抗炎药物,并被证明具有神经保护作用。这项工作的目的是确定预防性使用UTI是否可以减轻ket诱导的认知障碍。在WMZ和OFT测试中发现,重复KET麻醉导致青春期小鼠认知和情绪障碍,而UTI预处理逆转了与AK组相比较差的表现,CK+UTI组的平台寻找时间和中心穿越时间明显短(P < 0.05)。我们的ELISA实验结果发现,与AK相比,UTI预处理降低了CK麻醉诱导的IL-1β和IL-6的表达水平(P < 0.05)。此外,与AK组相比,UTI预处理通过抑制CK组Tau蛋白、Tau磷酸化-396蛋白和Aβ蛋白的表达水平来保护认知功能(P < 0.05)。提示UTI可作为预防KET神经毒性的新策略,显示UTI具有显著的神经保护作用。
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Ulinastatin Alleviates Repetitive Ketamine Exposure-Evoked Cognitive Impairment in Adolescent Mice.

Ketamine (KET) is widely used for induction and maintenance of anesthesia, and long-term use is required for treatment of depression patients. Repeated use of KET is associated with mood and memory disorders. Ulinastatin (UTI), a urinary trypsin inhibitor, has been widely undertaken as an anti-inflammatory drug and proved to have neuroprotective effects. The aim of this work was to determine whether prophylactic use of UTI could attenuate KET-induced cognitive impairment. It was found that repetitive KET anesthesia cause cognitive and emotional disorders in adolescent mice in WMZ and OFT test, while UTI pretreatment reversed the poor performance compared to the AK group, and the platform finding time and center crossing time were obviously short in the CK+UTI group (P < 0.05). Our ELISA experiment results discovered that UTI pretreatment reduced the expression levels of IL-1β and IL-6 induced by CK anesthesia compared to AK (P < 0.05). In addition, UTI pretreatment protected the cognitive function by restraining the expression levels of Tau protein, Tau phospho-396 protein, and Aβ protein in the CK group compared to the AK group in Western blotting (P < 0.05). The results suggested that UTI could act as a new strategy to prevent the neurotoxicity of KET, revealing a significant neuroprotective effect of UTI.

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来源期刊
Neural Plasticity
Neural Plasticity NEUROSCIENCES-
CiteScore
6.80
自引率
0.00%
发文量
77
审稿时长
16 weeks
期刊介绍: Neural Plasticity is an international, interdisciplinary journal dedicated to the publication of articles related to all aspects of neural plasticity, with special emphasis on its functional significance as reflected in behavior and in psychopathology. Neural Plasticity publishes research and review articles from the entire range of relevant disciplines, including basic neuroscience, behavioral neuroscience, cognitive neuroscience, biological psychology, and biological psychiatry.
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