Esketamine mediated AMPK/PAK2 signaling pathway to regulate endoplasmic reticulum stress to improve postoperative cognitive dysfunction in rats
Objective To investigate the effects of esketamine on the regulation of endoplasmic reticulum stress by AMPK/PAK2 signaling pathway on postoperative cognitive dysfunction(POCD)in rats.Methods Thirty SD rats aged 20 months were randomly divided into control group(Control group),model group(POCD group)and esketamine group(Esketamine group).The model group was prepared by internal fixation of tibial fracture.Morris water maze test was used to evaluate the cognitive function of rats.HE staining was used to observe the pathological changes of hippocampus.ELISA was used to detect the levels of GSH,SOD and MDA in serum,and immunofluorescence was used to detect the levels of ROS in hippocampus of brain tissue.The expressions of PERK,ATF6,CHOP,AMPK,p-AMPK and PAK2 were detected by Western blot.Results In the Morris water maze experiment,the escape latency of rats in esketamine group was shortened,the times of crossing the original platform area and the time in the original platform quadrant were significantly increased,the structure of nerve cells in hippocampus of rat brain was improved and the damage was alleviated,the oxidative stress response of rats was decreased,ROS production was decreased in hippocampus,endoplasmic reticulum stress was decreased.Conclusion Esketamine might mediate AMPK/PAK2 signaling pathway to regulate endoplasmic reticulum stress and improve postoperative cognitive dysfunction in rats.
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