| BackgroundPatients often have experienced some stressful events before anesthesia such as preoperative anxiety and fear, car accidents, trauma, or acute respiratory distress shortly before induction of general anesthesia which would have a huge effect on patients both physically and mentally once they became stable long-term memory. So it's very important and very meaningful to know how to prevent these harmful information from turning into long-term memory. Propofol is commonly used for general anesthesia and for sedation for patients undergoing intensive care unit(ICU). So it's crucial to investigate the effect of propofol on fear memory. Results of previous researches about the effect of propofol on fear memory were different. On the one hand, some researches showed that propofol could impair the formation of fear memory. For example, Gorman et al reported that propofol could impair the formation of fear memory when adult male wistar rats received propofol 150mg/kg administered intraperitoneally in 3 hours after inhibitory avoidance training. And Semba et al even found that fear memory would be impaired when adult male wistar rats received propofol 60mg/kg administered intraperitoneally immediately after inhibitory avoidance training. On the other hand, some studies showed that propofol would not interfere with the formation of fear memory. Instead, it would enhance the formation of fear memory. For example, a latest research from roman university showed that the latency of 48-h inhibitory avoidance performance would be significantly increased when adult male Sprague-dawley rats received propofol 300mg/kg or 350mg/kg administered intraperitoneally in 30 min after inhibitory avoidance training. So the real effect of propofol on fear memory deserve further study.The mechanism of the effect of agents used for general anesthesia on fear memory are still unknown. Previous studies mainly focused on the effect of general anesthetics on the key proteins related to the formation of fear memory. However, as we all know, the function of proteins rely on its functional state and its level. And translational modification is one important factor that could influence the functional state of proteins. The forms of translational modification contain phosphorylation, acetylation, sumoylation, ubiquitination and so on. Ubiquitination could not only influence the functional state of proteins but also influence the amount of proteins. Besides many researches show that the ubiquitin proteasome system plays an important role in the formation of fear memory. So whether the ubiquitin proteasome system plays an important role in the effect of propofol on the formation of fear memory deserve our study.MethodsIn the first part, we aim at revealing the effect of propofol on the formation of memory. Sixteen adult male Sprague-Dawley rats were randomizedly divided into two groups: group N and group P. Rats in the group N received N.S. 15ml/kg administered intraperitoneally immediately after inhibitory avoidance training. Rats in the group P received propofol 150mg/kg administered intraperitoneally immediately after inhibitory avoidance training. 24 hours' later, the retention test was performed.In the second part, we aim at exploring the effect of propofol on the level of ubiquitination of proteins in the hippocampus of rats. Fifteen adult male Sprague-Dawley rats were randomizedly divided into three groups: group Nv,group N and group P. Rats in the group Nv received no inhibitory training and drugs infusion. Rats in the group N received N.S. 15ml/kg administered intraperitoneally immediately after inhibitory avoidance training and the hippocampus was isolated 1h after inhibitory avoidance training.Rats in the group P received propofol 150mg/kg administered intraperitoneally immediately after inhibitory avoidance training and the hippocampus was isolated 1h after inhibitory avoidance training.In the third part, we aim at exploring the role of ubiquitination of proteins in the hippocampus of rats in the effect of propofol on the formation of fear memory. Forty adult male rats were randomizedly divided into four groups: group D+N, group D+P, group R+N and group R+P after surgery. Rats in the group D+N received DMSO 0.5ul/side administered intracranially 5 min before IA training and N.S. 15ml/kg administered intraperitoneally immediately after IA training. The retention test was performed 24 h later. Rats in the group D+P received DMSO 0.5ul/side administered intracranially 5 min before IA training and propofol 15omg/kg administered intraperitoneally immediately after IA training. The retention test was performed 24 h later. Rats in the group R+N received PYR41(200umol/ul) 0.5ul/side administered intracranially 5 min before IA training and N.S. 15ml/kg administered intraperitoneally immediately after IA training. The retention test was performed 24 h later. Rats in the group R+P received PYR41(200umol/ul) 0.5ul/side administered intracranially 5 min before IA training and propofol 150mg/kg administered intraperitoneally immediately after IA training. The retention test was performed 24 h later. Meanwhile,we also explored the effect of PYR41 on the level of ubiquitination of proteins in the hippocampus of rats. Twenty adult male rats were divided into four groups: group D+N, group D+P,group R+N and group R+P after surgery. Rats in in the group D+N received DMSO 0.5ul/side administered intracranially 5 min before IA training and N.S. 15ml/kg administered intraperitoneally immediately after IA training and the hippocampus was isolated in 1h after IA training.Rats in the group D+P received DMSO 0.5ul/side administered intracranially 5 min before IA training and propofol 15omg/kg administered intraperitoneally immediately after IA training and one hour later the hippocampus was isolated. Rats in the group R+N received PYR41(200umol/ul) 0.5ul/side administered intracranially 5 min before IA training and N.S. 15ml/kg administered intraperitoneally immediately after IA training and the hippocampus was isolated in 1h after IA training. Rats in the group R+P received PYR41(200umol/ul) 0.5ul/side administered intracranially 5 min before IA training and propofol 150mg/kg administered intraperitoneally immediately after IA training. The hippocampus was isolated in 1h after IA training.In the fourth part, we aim at exploring the the form of ubiquitination of proteins in the hippocampus.ResultsThe latencyof 24-h inhibitory performance would be decreased significantly compared with the corresponding vehicle group when adult male Sprague-dawley rats received propofol 150mg/kg administered intraperitoneally immediately after the IA training.The level of ubiquitination of proteins in the hippocampus would be increased significantly in one hour if adult male Sprague-dawley rats received propofol 150mg/kg administered intraperitoneally immediately after the IA training. And such kind of ubiquitination were not K48-linked specified. And PYR41 could attenuate the impairment of memory formation of propofol via reversing the change of the level of ubiquitination of proteins in the hippocampus of rats. Conclusions Collectively, these findings support the hypothesis that propofol could impair the formation of fear memory in rats and propofol-induced impairment of memory may be due, at least in part, to the increasing of the level of poly-ubiquitination in the hippocampus. |
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