Objective To evaluate the effects of sevoflurane on the expression of early growth response gene 1 (Egr-1) and Egr-2 in the suprachiasmatic nuclei (SCN) of sleep-deprived rats.Methods Forty-eight pathogen-free healthy male Sprague-Dawley rats,were divided into 4 groups (n =12 each) using a random number table:control group (group C),sleep deprivation group (group SD),sevoflurane group (group SEV) and sleep deprivation plus sevoflurane group (group SD+SEV).The rats were subjected to sleep deprivation for 96 h in group SD.The rats inhaled 2.5％ sevoflurane for 3 h in group SEV.The rats inhaled 2.5％ sevoflurane for 3 h after being subjected to sleep deprivation for 96 h in group SD+SEV.The mechanical paw withdrawal threshold (MWT) was measured at 12 h,3 days and 7 days after emergence from anesthesia (T1-3).The animals were sacrificed after blood samples were obtained from the external carotid artery,and the cerebral SCN was removed for determination of Egr-1 and Egr-2 expression by Western blot.Results Compared with group C,the MWT was significantly decreased at T1-3 in SD,SEV and SD+SEV groups,the expression of Egr-1 and Egr-2 in SCN was significantly up-regulated at T1-3 in SD and SD+SEV groups,and the expression of Egr-1 in SCN was significantly up-regulated at T1-3,and the expression of Egr-2 in SCN was up-regulated at T1 in group SEV (P＜0.05).Compared with SD and SEV groups,the MWT was significantly decreased at T1-3 in group SD+SEV,and the expression of Egr-1 and Egr-2 in SCN was significantly up-regulated at T1-3 in group SD+SEV (P＜0.05).Conclusion The mechanism by which sevoflurane aggravates hyperalgesia is related to up-regulation of Egr-1 and Egr-2 expression in SCN of sleepdeprived rats.

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.

Objective: To investigate the role of clock gene Bmal1, Per2 and Egr1 expression in learning and memory undergoing sevoflurane anesthesia after acute sleep deprivation. Methods: 72 male SD rats were equally divided into four groups using a random number table (n=18) : normal control group (group Control), do not do any processing; sleep deprivation group (group SD), acute sleep deprivation for 96 h; sevoflurane group (group Sev), suffering 2.5% sevoflurane for 3 h; sleep deprivation+sevoflurane group (group SD+Sev), 96 h sleep deprivation followed by 3 h 2.5% sevoflurane inhalation. The Morris water maze, for spatial memory acquisition test, was used to measure the time percent of target quadrant and numbers of platform-site crossovers before sleep deprivation (T0) and at 1 d (T1), 3 d (T2), 7 d (T3) after inhalation anesthesia. Rats were sacrificed after spatial memory acquisition test. Brain hippocampus samples were obtained for determination of Bmal1, Per2 and Egr1 expression by Western blot, and neuron morphology was observed by the Nissl staining. Results: Compared with Control group, the percentage of time in target quadrant and the numbers of platform-site crossovers were significantly decreased at T1 and T2 in Sev group (P<0.05); and compared with Control group, the percentage of time in target quadrant and the numbers of platform-site crossovers were also significantly decreased at T1, T2 and T3 in SD group rats (P<0.05). Compared with Sev group rats (the percentages of time in target quadrant: T1: (32.37±1.36)%; T2: (30.91±1.26)%; T3: (33.78±2.20)%; the numbers of platform-site crossovers: T1: (4.55±0.39); T2: (3.11±0.37); T3: (3.95±0.34)), the percentages of time in target quadrant (T1: (27.20±1.42)%; T2: (28.19±1.04)%; T3: (30.06±1.22)%) and the numbers of platform-site crossovers (T1: (3.11±0.46); T2: (3.30±0.38); T3: ( 3.20±0.39)) in SD+Sev group rats were significantly decreased at T1, T2 and T3 (all P<0.05). Compared with control group, the levels of hippocampal proteins Bmal1, Per2 and Egr1 were significantly reduced at T1 in Sev group (P<0.05). Compared with control group, the level of hippocampal protein Per2 was significantly increased, but the levels of hippocampal proteins Bmal1 and Egr1 were significantly decreased at T1 and T2 in SD group (P<0.01). Compared with Sev group, the levels of hippocampal proteins Bmal1 and Egr1 were significantly reduced at T1, T2 and T3 in SD+Sev group (P<0.01), and the protein level of hippocampal Per2 was significantly decreased at T1, but then increased at T2 and T3 in SD+Sev group (P<0.01). The hippocampal Nissl staining in CA1 at T2 revealed that there were irregular distribution of pyramidal neurons existed in Sev group, and vacuolar degeneration with vague outlines of pyramidal neurons in SD group, while pyramidal neuron atrophy and few number of Nissl bodies, compared with control group, were observed in SD+Sev group. Conclusion Acute sleep deprivation following with sevoflurane anesthesia resulted in hippocampal memory impairment, which was associated with abnormal expression of hippocampal Bmal1, Per2 and Egr1.

MiR-142-3p has been reported to act as a tumor suppressor in breast cancer. However, the regulatory effect of miR-142-3p on drug resistance of breast cancer cells and its underlying mechanism remain unknown. Here, we found that miR-142-3p was significantly downregulated in the doxorubicin (DOX)-resistant MCF-7 cell line (MCF-7/DOX). MiR-142-3p overexpression increased DOX sensitivity and enhanced DOX-induced apoptosis in breast cancer cells. High-mobility group box 1 (HMGB1) is a direct functional target of miR-142-3p in breast cancer cells and miR-142-3p negatively regulated HMGB1 expression. Moreover, overexpression of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by miR-142-3p up-regulation. In conclusion, miR-142-3p overexpression may inhibit autophagy and promote the drug sensitivity of breast cancer cells to DOX by targeting HMGB1. The miR-142-3p/HMGB1 axis might be a novel target to regulate the drug resistance of breast cancer patients.