关键词: 依托咪酯, MAPK/ERK信号通路, 阿尔茨海默病, 认知功能, 氧化应激

Abstract: Objective　To investigate the effects of etomidate on cognitive function and oxidative stress in Alzheimer's disease mice by regulating mitogen-activated protein kinase (MAPK) / extracellular signal-regulated kinase (ERK) signaling pathway. Methods　The study was conduct from May 2020 to September 2021.In this study, fifty APP/PS1 transgenic mice were divided into a model group, low, medium, and high dose of etomidate groups, and a positive control group, ten SPF grade C57BL/6 mice were used as control. Among them, the low, medium, and high dose of etomidate groups were given gavage with 1.0, 2.5, and 5.0 mg/kg of etomidate, the positive control group was given gavage with 10 mg/kg of donepezil hydrochloride, and the model group and control group were given gavage with an equal volume of normal saline, 1 time/d, for 30 d. The Morris water maze test was used to observe the learning and memory abilities of the mice, and the nerve injury score and brain tissue water content of the mice were measured; Western blot was used to detect the expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-10, IL-1β, and MAPK/ERK signaling pathway-related proteins in mouse brain tissue; enzyme-linked immunosorbent assay (ELISA) was used to detect the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA) in mouse brain tissue. One-way analysis of variance was used to compare the measurement data among multiple groups, and LSD-t test was used for further pairwise comparison. Results　Compared with those of the control group, the escape latency of the model group was significantly prolonged, the number of cross-platforms, the platform area stay distance, and the activities of SOD, CAT, and GSH-Px were decreased, the nerve injury score, brain tissue water content, and MDA content were increased, the protein expressions of TNF-α, IL-10, and IL-1β were up-regulated, and the protein expressions of phosphorylated extracellular signal-regulated kinase (p-ERK) 1/2 and p-p38 were down-regulated (all P<0.05). Compared with those of the model group, the escape latency of the low, medium, and high dose of etomidate groups were significantly shortened, the numbers of cross-platform, platform area stay distances, and activities of SOD, CAT, and GSH-Px were increased, the nerve injury scores, brain tissue water contents, and MDA contents were decreased, the protein expressions of TNF-α, IL-10, and IL-1β were down-regulated, and the protein expressions of p-ERK1/2 and p-p38 were up-regulated (all P<0.05). Conclusion　Etomidate may improve the cognitive function in Alzheimer's disease mice by increasing MAPK/ERK signaling pathway, and reduce the oxidative stress and inflammatory response in mouse brain tissue.

Key words: Etomidate, MAPK/ERK signaling pathway, Alzheimer's disease, Cognitive function, Oxidative stress