Regulating effect of REV-ERBα on working memory after laparotomy and its mechanism in rats exposed to sleep deprivation
10.3760/cma.j.cn115354-20191217-00753
- VernacularTitle: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
- Author:
Jiabao HOU
1
;
Xing WAN
;
Qianni SHEN
;
Xuke LIU
;
Yang WU
;
Wenqin SONG
;
Zhongyuan XIA
;
Bo ZHAO
Author Information
1. 武汉大学人民医院麻醉科，武汉 430060
- Keywords:
Sleep deprivation;
Exploratory laparotomy;
Working memory;
Neuroinflammation;
REV-ERBα
- From:
Chinese Journal of Neuromedicine
2020;19(3):253-259
- CountryChina
- Language:Chinese
-
Abstract:
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+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.
