Role of hippocampal REV-ERBα in postoperative cognitive dysfunction in rats / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of hippocampal REV-ERBα in postoperative cognitive dysfunction in rats.Methods:Thirty-two SPF healthy male Sprague-Dawley rats, aged 12-14 weeks, weighing 360-380 g, were divided into 4 groups ( n=8 each) using a random number table method: control group (group C), surgery group (group S), surgery + dimethyl sulfoxide (DMSO) group (group SD), and surgery + SR9009 group (group SS). Exploratory laparotomy was performed under sevoflurane anesthesia in S, SD and SS groups.Normal saline containing 0.1% DMSO was injected into hippocampal CA1 area at 1 h before laparotomy, with 2 μl on each side in group SD, and REV-ERBα agonist SR9009 (in normal saline containing 0.1% DMSO) was injected into hippocampal CA1 area at 1 h before laparotomy, with 2 μl on each side in group S+ SR9009.Morris water maze test was performed at 1 and 3 days after operation.Rats were sacrificed at 1 h after the end of Morris water maze test on day 3 after surgery, and the hippocampal tissues were obtained for determination of the expression of REV-ERBα, Brain and Muscle ARNT-Like 1 (BMAL1) protein, synaptophysin (SYN), postsynaptic density (PSD)-95 protein and N-methyl-D-aspartate receptor 2B subunit (GRIN2B) (by Western blot) and microscopic examination of the morphology of hippocampal neurons and Nissl bodies (by Nissl staining), and the viable neurons were counted. Results:Compared with group C, the percentage of time of staying at the target quadrant was significantly decreased, and the number of crossing platform was reduced on days 1 and 3 after exploratory laparotomy, the expression of REV-ERBα, BMAL1, PSD95, SYN and GRIN2B was down-regulated, and the number of viable neurons was decreased in group S and group SD ( P<0.05). Compared with group S and group SD, the percentage of time of staying at the target quadrant and the number of crossing platform were significantly increased on days 1 and 3 after exploratory laparotomy, the expression of REV-ERBα and PSD95 was up-regulated, the number of viable neurons was increased ( P<0.05), and no significant change was found in the expression of BMAL1, SYN and GRIN2B in group SS ( P>0.05). There was no significant difference in the indexes mentioned above between group S and group SD ( P>0.05). Conclusions:Activation of REV-ERBα can improve postoperative cognitive dysfunction, and the mechanism may be related to up-regulation of PSD95 expression in hippocampus and reduction of neuronal damage in rats.