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查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+剖腹探查手术+SR9009组，每组18只。睡眠剥夺组、剖腹探查手术组、睡眠剥夺+剖腹探查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+剖腹探查手术+SR9009组大鼠给予REM睡眠剥夺96 h后行剖腹探查手术，术后当天到术后第5天每天腹腔注射100 mg/kg SR9009。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查手术组；术后第2、3、4、5天睡眠剥夺+剖腹探查手术+SR9009组大鼠的对位逃避潜伏期短于睡眠剥夺+剖腹探查手术组，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+剖腹探查手术组海马组织中REV-ERBα、BMAL1蛋白的表达降低，IL-1β和IL-6的水平增高；与睡眠剥夺+剖腹探查手术组比较，睡眠剥夺+剖腹探查手术+SR9009组大鼠海马组织中REV-ERBα、BMAL1蛋白的表达增加，IL-1β和IL-6的水平降低，差异均有统计学意义( P<0.05)。(3)与对照组比较，剖腹探查手术组、睡眠剥夺组、睡眠剥夺+剖腹探查手术组大鼠海马CA3区神经元数量减少、星形胶质细胞活化增加；与睡眠剥夺+剖腹探查手术组比较，睡眠剥夺+剖腹探查手术+SR9009组大鼠海马CA3区神经元数量增加、星形胶质细胞活化减弱。 结论:急性REM睡眠剥夺模型大鼠行剖腹探查手术可导致海马工作记忆的损伤，其可能与海马REV-ERBα、BMAL1表达的下降和炎症反应的增加有关，使用SR9009可降低损害。

abstractsObjective: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+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 6 th d of surgery. The reversall escape latency of rats was recorded by contrapuntal space exploration training one-5 d after surgery. On the 5 th 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, 2 nd, 3 rd, 4 th, 5 th 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 2 nd, 3 rd, 4 th, 5 th d of surgery, the reversal escape latency in the sleep deprivation+exploratory laparotomy+SR9009 group was statistically shorter than that in the sleep deprivation+exploratory laparotomy group ( P<0.05). The number of times of rats crossing the original platform in the sleep deprivation group, exploratory laparotomy group, and sleep deprivation+exploratory laparotomy group was significantly smaller than that of the control group ( P<0.05); that of rats in the sleep deprivation+exploratory laparotomy group was significantly smaller than that of the exploratory laparotomy group, and that of rats in the sleep deprivation+exploratory laparotomy+SR9009 group was significantly larger than that of the sleep deprivation+exploratory laparotomy group ( P<0.05). (2) As compared with the control group, the exploratory laparotomy group, sleep deprivation group and sleep deprivation+exploratory laparotomy group had significantly decreased expressions of REV-ERBα and BMAL1, and statistically increased IL-1β and IL-6 levels in the hippocampal tissues ( P<0.05); as compared with the sleep deprivation+exploratory laparotomy group, the sleep deprivation+exploratory laparotomy+SR9009 group had significantly increased expressions of REV-ERBα and BMAL1, and statistically decreased IL-1β and IL-6 levels ( P<0.05). (3) As compared with the control group, the exploratory laparotomy group, sleep deprivation group and sleep deprivation+exploratory laparotomy group had decreased amount of neurons in the hippocampal CA3 area and increased amount of activated astrocytes; as compared with the sleep deprivation+exploratory laparotomy group, the sleep deprivation+exploratory laparotomy+SR9009 group had increased amount of neurons in the hippocampal CA3 area and decreased amount of activated astrocytes. Conclusion:Acute REM sleep deprivation can lead to work memory impairment in rats accepted exploratory laparotomy, which might be associated with neuroinflammation and REV-ERBα/BMAL1 pathway, and SR9009 could alleviate the damage.