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自噬抑制剂3-甲基腺嘌呤可恢复七氟醚麻醉诱导的认知功能障碍和神经元凋亡。

The autophagy inhibitor 3-methyladenine restores sevoflurane anesthesiainduced cognitive dysfunction and neurons apoptosis.

作者信息

Xiao Xiaoyu, Zhu Yingxian, Bu Juyuan, Li Guowei, Liang Zibin, Yang Lukun, Hou Bingzong

出版信息

Pharmazie. 2017 Apr 1;72(4):214-218. doi: 10.1691/ph.2017.6872.

Abstract

This study was designed to explore the effect of 3-methyladenine (3-MA) on sevoflurane anesthesia-induced cognitive dysfunction. A total of 60 C57BL/6 (5-8 months old) mice were randomly arranged into 3 groups: Control, sevoflurane (Sev) and Sev+3-MA group with 3-MA administration was performed during Sev administration. Morris water maze and Y-maze test were performed to examine the behavioral disorders. Moreover, hippocampal neuronal cell apoptosis and expression of autophagy related genes were detected. Sevoflurane induced cognitive dysfunction in mice showing significant longer escape latency, lower number of correct response, higher apoptotic neurons, and higher expression of autophagy related genes. However, additional 3-MA administration inhibited the effect of sevoflurane on cognitive dysfunction by shorting escape latency, reducing correct response number, inhibiting neurons apoptosis and autophagy genes expression. 3-MA additional administration inhibited sevoflurane anesthesia-induced cognitive dysfunction on mice. 3-MA might be usefull as an inhibitor for sevoflurane anesthesia-induced cognitive dysfunction in clinical trials.

摘要

本研究旨在探讨3-甲基腺嘌呤(3-MA)对七氟醚麻醉诱导的认知功能障碍的影响。总共60只C57BL/6小鼠(5 - 8月龄)被随机分为3组:对照组、七氟醚组(Sev)和Sev + 3-MA组,在七氟醚给药期间给予3-MA。进行莫里斯水迷宫和Y迷宫试验以检测行为障碍。此外,检测海马神经元细胞凋亡和自噬相关基因的表达。七氟醚诱导小鼠认知功能障碍,表现为显著更长的逃避潜伏期、更低的正确反应次数、更高的凋亡神经元以及更高的自噬相关基因表达。然而,额外给予3-MA通过缩短逃避潜伏期、减少正确反应次数、抑制神经元凋亡和自噬基因表达来抑制七氟醚对认知功能障碍的影响。额外给予3-MA可抑制七氟醚麻醉诱导的小鼠认知功能障碍。在临床试验中,3-MA可能作为七氟醚麻醉诱导的认知功能障碍的抑制剂有用。

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