| Intravenous anesthetics propofol is commonly used. But in the widely used,propofol is found in forgetting effect, may be the cause of postoperative cognitivedysfunction (POCD) inducement. POCD is a common complication of centralnervous system of clinical after operation, the incidence rate has been high, but theprecise mechanism is not yet clear. Age is currently the only specific risk factor ofPOCD. Hippocampus is mainly responsible for learning and memory, spatialpositioning functions, and synaptic plasticity is in close relationship with it. The mainmanifestation of synaptic plasticity forming is long term potentiation (LTP) andlong-term depression (LTD). They are believed to be the neural basis of learning andmemory. Biological clock gene has control effect on plasticity of neuron and learningand memory. Relationship between mechanisms of propofol induced POCD andbiological clock gene is not clear. This experiment investigates the effects of propofolon cognitive function and hippocampal biological clock genes, and provides referencefor further clinical research.By this experiment, the effect of propofol on the aged male rats learning memoryability and the expression of circadian genes in hippocampus is observed, toinvestigate the relationship between mechanisms of propofol induce POCD and thecircadian clock genes.Method:72elderly male SD rats weighting500g-550g were randomly divided into3groups, propofol30mg/(kg·h) group, propofol50mg/(kg·h) group and control group,24rats in each group. Propofol30mg/(kg h) group and propofol50mg/(kg h) groupwere intravenously injected with propofol four hours at each dose, and the controlgroup avoided the stress for four hours. When rats awake,0h,4h,24h and72h later,6rats is randomly selected of each group for Morris water maze to test the spatial learning and memory, after test, the rats were killed by decapitation to takehippocampus tissues, the total RNA was extracted, then use real-time quantitativepolymerase chain reaction (RT-qPCR) to analyze expression of Per2, Dbp, Arc, Egr1,Krox20and NGFI-B.Results:1.Morris water maze test results:(1) navigation experiment: after anesthesia, P30group and P50group latency than C group, the difference was statistically significant(P <0.05), and the prolonged of incubation period of P50group is more obviouslythan P30group (P <0.05); P30group after operation, compare the differencesbetween0h and4H24h point in time and preoperative has statistical significance (P <0.05); the difference was statistically significant after anesthesia compared withpreoperative P50group (P <0.05).(2) the spatial probe test results: preoperative ratsthrough the original platform number, no significant difference (P>0.05); P30groupand P50group through the original platform times than in the C group decreased (P <0.05), P50group through the original platform times than in the P30group decreasedmore obviously comparison of72h(P <0.05); postoperative time points and24h afteroperation, P30group and P50group through the original platform number increased(P <0.05).The Results of quantitative detection of RT-qPCR (1): the Per2gene of P30group and P50group after0h,4h,24h and C groups, the expression amount decreased(P <0.05), expression of P50group than in P30group per2decreased more obviously(P <0.05), with the extension of time, narrowing differences, no significantdifferences between the P30group and the C group24h after operation (P>0.05),P50group72h after operation as compared with C group, the expression of Per2genein less;(2): Arc expression level of Arc gene P30and P50in the comparison ofpostoperative0h,4H and decreased in the C group (P <0.05);24hours after operationin P30group compared with C group, the difference was not statistically significant (P>0.05), P50after the operation of group72h compared with group C, the expressionofArc and less (P <0.05).(3) the EGR1gene: P30and P50in postoperative0h,4H ofEGR1expression was reduced (P <0.05); postoperative24hours P30group and C group were compared statistically significant (P>0.05), P50group after72h andgroup C and P30group compared the expression of EGR1less (P <0.05).(4) NGFI-beta gene: P30group and p50group at postoperative0h,4h,24h and group Ccompared NGFI-beta expression decreased, and p50group than the P30groupdecreased significantly (P <0.05); postoperative72hours P30group and p50groupand group C compared, and differences have no statistical significance (P>0.05).(5)DBP gene: P30group and p50group at postoperative0h,4h,24h and group Ccompared increased the expression of DBP (P <0.05), and the expression of P50group than P30group DBP increased more significantly (P <0.05),72h after theoperation of P30group and p50group and group C compared statistically significant(P>0.05).(6) Krox20gene: Krox20gene: P30and p50after each time point in groupC compared Krox20expression was significantly reduced (P <0.05), P30group andp50group compared statistically significant (P>0.05).Conclusions:1propofol intravenous anesthesia can injure spatial learning and memory abilityof rats, the large dose of medicine may aggravate this injury, but it can be recovered ina short time.2. Propofol can affect the expression of circadian clock genes. It may beassociated with propofol induced POCD.Innovation point：Selected aged male rats are treated with continuous intravenous pump, which isclosely to the actual clinical mode. we compare30mg/(kg·h) and50mg/(kg·h)dose of intravenous infusion of propofol continued for4h, respectively, in the wake of0h,4h,24h and72h, four different time points by Morris water maze test, from theangle of behavior, to observe the changes of spatial learning and memory ability inrats, and then real-time quantitative fluorescence PCR is performed to detect relatedgenes. Finally, through comprehensive analysis of the influence of propofol on spatiallearning and memory in rats and its mechanism, references for clinical medication andprevention of POCD is provided. |
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