艾司氯胺酮介导AMPK/PAK2信号通路调节内质网应激改善大鼠术后认知功能障碍  

Esketamine mediated AMPK/PAK2 signaling pathway to regulate endoplasmic reticulum stress to improve postoperative cognitive dysfunction in rats

作　　者：王睿[1] 李闯[1] 张明宇 曹芳榕 孙晓峰[1] WANG Rui;LI Chuang;ZHANG Ming-yu;CAO Fang-rong;SUN Xiao-feng(Department of Anesthesiology,Central Hospital Affiliated to Shenyang Medical College,Shenyang 110024;Department of Anesthesiology,The First Medical Center of PLA General Hospital,Beijing 100853,China)

机构地区：[1]沈阳医学院附属中心医院麻醉科,辽宁沈阳110024 [2]解放军总医院第一医学中心麻醉科,北京100853

出　　处：《解剖科学进展》2024年第2期157-160,共4页Progress of Anatomical Sciences

基　　金：沈阳医学院硕士研究生科技创新基金(Y20220532)。

摘　　要：目的探讨艾司氯胺酮介导AMPK/PAK2信号通路调节内质网应激改善大鼠术后认知功能障碍(POCD)。方法30只雄性20月龄SD大鼠,随机分为对照组(Control),模型组(POCD)和艾斯氯胺酮处理组(Esketamine),使用胫骨骨折内固定法制备模型。Morris水迷宫实验评价各组大鼠认知功能,HE染色观察大鼠海马病理变化情况,ELISA检测大鼠血清中炎症因子GSH、SOD和MDA含量,免疫荧光检测大鼠脑组织海马区ROS含量,Western blot法检测大鼠脑海马组织PERK、ATF6、CHOP、AMPK、p-AMPK和PAK2蛋白表达。结果经艾斯氯胺酮处理后的大鼠,在Morris水迷宫实验中缩短逃避潜伏期、穿越原平台区域次数与在原平台所在象限的时间均显著增加;大鼠脑组织海马区神经细胞结构有所改善,损伤减轻;大鼠氧化应激反应降低;脑组织海马区ROS生成减少;内质网应激降低。结论艾司氯胺酮可能介导AMPK/PAK2信号通路调节内质网应激改善大鼠术后认知功能障碍。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.

关 键 词：术后认知功能 艾斯氯胺酮 AMPK PAK2 内质网应激 

分 类 号：R749.6[医药卫生—神经病学与精神病学]