Department of Anesthesiology and Pain Medicine, School of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Republic of Korea.
Department of Pharmacology, School of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Republic of Korea.
Brain Res. 2018 Dec 1;1700:99-108. doi: 10.1016/j.brainres.2018.07.007. Epub 2018 Jul 10.
Propofol is the most widely accepted intravenous anesthetic available for clinical use. However, neurotoxicity of propofol in the developing brain has been reported. This study investigated the effects of propofol on cognitive function in normal healthy adult mice. Thirty-three GFP-LC3 adult mice were included. Propofol was injected for anesthesia (n = 22). The sham control (n = 11) received intralipid injections. The mice completed a Y-maze test on 3 and 7 days after being anesthetized. Western blotting, immunofluorescence staining, and transmission electron microscopic (TEM) analyses were performed with their hippocampi. In addition, we conducted a separate ex vivo experiment using organotypic hippocampal slice cultures (OHSCs) to investigate the effects of propofol on induced autophagy. There was a significantly lower percentage of alternation in the Y-maze test on day 3 after propofol anesthesia than the control, but no difference was observed on day 7. Western blot analyses and immunofluorescence assays showed that the levels of cognitive function-related proteins significantly decreased in the propofol group compared to the control on day 3 but had recovered by day 7. In terms of autophagy-related proteins, western blot analyses and immunofluorescence assays showed that propofol increased autophagic induction, flux, and degradation of autophagosomes. Ex vivo experiments showed that propofol enhanced autophagic flux of the induced autophagy. In conclusion, although transient cognitive dysfunction occurred, adult mice recovered their cognitive function after the administration of propofol anesthesia. And this finding may be associated with enhanced autophagic flux.
异丙酚是目前临床应用最广泛的静脉麻醉剂。然而，已有研究报道异丙酚具有神经毒性。本研究旨在探讨异丙酚对正常成年小鼠认知功能的影响。共纳入 33 只 GFP-LC3 成年小鼠。其中 22 只小鼠接受异丙酚麻醉（n = 22），11 只接受脂肪乳剂注射（假手术对照，n = 11）。麻醉后 3 天和 7 天，小鼠完成 Y 迷宫测试。Western blot、免疫荧光染色和透射电镜（TEM）分析用于检测其海马组织。此外，我们还进行了一项独立的离体实验，使用器官型海马切片培养（OHSCs）来研究异丙酚对诱导自噬的影响。与对照组相比，异丙酚麻醉后 3 天的 Y 迷宫测试中交替百分比明显降低，但第 7 天无差异。Western blot 分析和免疫荧光检测显示，与对照组相比，异丙酚组认知功能相关蛋白水平在第 3 天显著降低，但在第 7 天恢复正常。自噬相关蛋白方面，Western blot 分析和免疫荧光检测显示，异丙酚诱导自噬增强，自噬体的自噬流和降解增加。离体实验表明，异丙酚增强了诱导自噬的自噬流。总之，虽然小鼠在接受异丙酚麻醉后出现短暂的认知功能障碍，但在麻醉后能够恢复认知功能。这一发现可能与增强的自噬流有关。
