REV-ERBα对睡眠剥夺大鼠剖腹探查手术后工作记忆的调控作用及其机制研究  

Regulating effect of REV-ERBα on working memory after laparotomy and its mechanism in rats exposed to sleep deprivation

作　　者：侯家保[1] 万杏[1] 沈倩妮[1] 刘旭珂 吴洋[1] 宋文沁 夏中元[1] 赵博[1] Hou Jiabao;Wan Xing;Shen Qianni;Liu Xuke;Wu Yang;Song Wenqin;Xia Zhongyuan;Zhao Bo(Department of Anesthesiology,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院麻醉科,武汉430060

出　　处：《中华神经医学杂志》2020年第3期253-259,共7页Chinese Journal of Neuromedicine

基　　金：中央高校基本科研业务费专项资金(2042019kf0061);武汉大学人民医院引导基金(RMYD2018M03)。

摘　　要：目的探讨REV-ERBα激动剂SR9009对急性快速眼球运动(REM)睡眠剥夺模型大鼠行剖腹探査手术后海马工作记忆的保护作用及其可能的机制。方法90只SD大鼠采用随机数字表法分为对照组、睡眠剥夺组、剖腹探查手术组、睡眠剥夺+剖腹探查手术组、睡眠剥夺+剖腹探査手术+SR9009组,每组18只。睡眠剥夺组、剖腹探查手术组、睡眠剥夺+剖腹探査手术组大鼠分别给予快速眼球运动(REM)睡眠剥夺96 h或(和)剖腹探查手术;睡眠剥夺+剖腹探査手术+SR9009组大鼠给予REM睡眠剥夺96h后行剖腹探查手术,术后当天到术后第5天每天腹腔注射100mg/kgSR9009。术后第1?5天行对位空间探索训练记录大鼠的对位逃避潜伏期。术后第5天行对位空间探索实验记录大鼠穿越原平台位置的次数;术后第3天Western blotting实验检测5组大鼠海马REV-ERBα和BMAL1蛋白的表达;酶联免疫吸附实验检测5组大鼠海马炎性因子白介素(IL)-1β和IL-6的水平;免疫荧光染色检测海马神经元核蛋白(NeuN)、胶质纤维酸性蛋白(GFAP)的表达。结果(1)术后第1、2、3、4、5天睡眠剥夺组、剖腹探查手术组、睡眠剥夺+剖腹探查手术组大鼠对位逃避潜伏期长于对照组;睡眠剥夺组和睡眠剥夺+剖腹探查手术组大鼠的对位逃避潜伏期长于剖腹探査手术组;术后第2、3、4、5天睡眠剥夺+剖腹探査手术+SR9009组大鼠的对位逃避潜伏期短于睡眠剥夺+剖腹探査手术组,差异均有统计学意义(P﹤0.05)。睡眠剥夺组、剖腹探查手术组、睡眠剥夺+剖腹探查手术组大鼠穿越原平台位置的次数少于对照组;睡眠剥夺+剖腹探查手术组大鼠穿越原平台位置的次数少于剖腹探查手术组,睡眠剥夺+剖腹探查手术+SR9009组大鼠穿越原平台的次数多于睡眠剥夺+剖腹探查手术组,差异均有统计学意义(P﹤0.05)。(2)与对照组比较,剖腹探查手术组、睡眠剥夺组和睡眠剥夺+剖腹探查手�Objective To investigate the protective effect of REV-ERBα agonist SR9009 on hippocampal working memory in rats with acute rapid eye movement(REM)sleep deprivation after exploratory laparotomy and its possible mechanism.Methods Ninety SD rats were randomly divided into control group,sleep deprivation group,exploratory laparotomy group,sleep deprivation+exploratory laparotomy group,and sleep deprivation+exploratory laparotomy十SR9009 group(n=18).Rats in the sleep deprivation group,exploratory laparotomy group,and sleep deprivation+exploratory laparotomy group were given REM sleep deprivation for 96 h or(and)exploratory laparotomy,respectively.Rats in the sleep deprivation+exploratory laparotomy+SR9009 group accepted exploratory laparotomy after REM sleep deprivation for 96 h,and accepted intraperitoneal injection of 100 mg/kg SR9009 daily from the day after surgery to the 6th d of surgery.The reversall escape latency of rats was recorded by contrapuntal space exploration training one-5 d after surgery.On the 5th d of surgery,reversal space exploration experiment was conducted to record the number of times of rats crossing the original platform.Western blotting was used to detect the protein expressions of REV-ERBα and BMAL1 in the hippocampus of rats.The levels of interleukin(IL)-1β and IL-6 in the hippocampus of rats were detected by enzyme-linked immunosorbent assay.Immunofluorescent staining was used to detect the expressions of neuronal nucleoprotein(NeuN)and glial fibrillary acidic protein(GFAP).Results(1)The escape latency in the sleep deprivation group,exploratory laparotomy group,and sleep deprivation+exploratory laparotomy group was significantly longer than that in the control group on the first,2nd,3rd,4th,5th d of surgery(P<0.05);while the escape latency in the sleep deprivation group and sleep deprivation+exploratory laparotomy group was significantly longer than that in the exploratory laparotomy group(P<0.05);on the 2nd,3rd,4th,5*d of surgery,the reversal escape latency in the sleep deprivation+

关 键 词：睡眠剥夺 剖腹探查手术 工作记忆 神经炎症 REV-ERBα 

分 类 号：R77[医药卫生—眼科]