Underlying Mechanisms of Memory Deficits Induced by Etomidate Anesthesia in Aged Rat Model: Critical Role of Immediate Early Genes

Xu Li; Fen Lu; Wei Li; Jun Xu; Xiao-Jing Sun; Ling-Zhi Qin; Qian-Lin Zhang

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Underlying Mechanisms of Memory Deficits Induced by Etomidate Anesthesia in Aged Rat Model: Critical Role of Immediate Early Genes

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Background: Etomidate (R-1-[1-ethylphenyl] imidazole-5-ethyl ester) is a widely used anesthetic drug that had been reported to contribute to cognitive deficits after general surgery.However, its underlying mechanisms have not been fully elucidated.In this study, we aimed to explore the neurobiological mechanisms of cognitive impairments that caused by etomidate.Methods: A total of 30 Sprague-Dawley rats were used and divided into two groups randomly to receive a single injection ofetomidate or vehicle.Then, the rats' spatial memory ability and neuronal survival were evaluated using the Morris water maze test and Nissl staining, respectively.Furthermore, we analyzed levels of oxidative stress, as well as cyclic adenosine 3',5'-monophosphate response element-binding (CREB) protein phosphorylation and immediate early gene (IEG, including Arc, c-fos, and Egr1) expression levels using Western blot analysis.Results: Compared with vehicle-treated rats, the etomidate-treated rats displayed impaired spatial learning (day 4:27.26 ± 5.33 s vs.35.52 ± 3.88 s, t =2.988, P =0.0068;day 5:15.84 ± 4.02 s vs.30.67 ± 4.23 s, t =3.013, P =0.0057;day 6:9.47 ± 2.35 s vs.25.66 ± 4.16 s, t =3.567, P =0.0036) and memory ability (crossing times: 4.40 ± 1.18 vs.2.06 ± 0.80, t =2.896, P =0.0072;duration: 34.00 ± 4.24 s vs.18.07 ± 4.79 s, t =3.023, P =0.0053;total swimming distance: 40.73 ± 3.45 cm vs.27.40 ± 6.56 cm, t =2.798, P =0.0086) but no neuronal death.Furthermore, etomidate did not cause oxidative stress or deficits in CREB phosphorylation.The levels of multiple IEGs (Arc: vehicle treated rats 100％, etomidate treated rats 86％, t =2.876, P =0.0086;c-fos: Vehicle treated rats 100％, etomidate treated rats 72％, t =2.996, P =0.0076;Egr1: Vehicle treated rats 100％, etomidate treated rats 58％, t =3.011, P =0.0057) were significantly reduced in hippocampi ofetomidate-treated rats.Conclusion: Our data suggested that etomidate might induce memory impairment in rats via inhibition of IEG expression.

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《中华医学杂志（英文版）》 |2016年第1期|48-53|共6页
作者
Xu Li; Fen Lu; Wei Li; Jun Xu; Xiao-Jing Sun; Ling-Zhi Qin; Qian-Lin Zhang;
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Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University, Henan Provincial Cancer Hospital, Zhengzhou, Henan 450008, China;

Department of Neurology, Affiliated People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China;

Department of Neurology, Affiliated People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China;

Department of Neurology, Affiliated People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China;

Department of Neurology, Affiliated People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China;

Department of Neurology, Affiliated People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China;

Department of Neurology, Affiliated People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China;

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Underlying Mechanisms of Memory Deficits Induced by Etomidate Anesthesia in Aged Rat Model: Critical Role of Immediate Early Genes

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