Study On The Correlation Between Dex And CX3CL1 Protein/receptor Expression Of Rats With POCD

Part I Experimental study on the effect of CX3CL1 protein/receptor expression changes in the occurrence of POCD in ratsBackground: Postoperative cognitive dysfunction(POCD)is a common postoperative complication of the central nervous system in elderly patients.The clinical manifestations of POCD are the ability decline of attention,memory,and computing powe.It may delay the patient’s recovery,prolong the length of hospital stay and increase the medical expenses,and even affect the patient’s quality of lif e after discharge.At present,the main research on the mechanism of POCD is the inflammatory response of the central nervous system,and the inflammatory response in the hippocampus is related to POCD to some extent.As an inhibitory chemotactic factor,CX3CL1 ACTS on the CX3CR1 receptor on microglia of the central system,which may regulate the release of inflammatory factors by microglia,thereby alleviating the occurrence and development of POCD.Objective: This experiment is to study the regulation of CX3CL1/ CX3CR1-mediated signaling pathway on microglia and the role of CX3CL1/ CX3CR1 in the occurrence of POCD.1.Through the establishment of POCD model to study the behavioral indicators of rats,the water maze method was used to detect the spatial memory ability of rats,to determine the changes of cognitive behavior before and after tibial fracture surgery.2.Changes in CX3CL1 expression in central inflammatory factors are detected when POCD is occurred in rats,and an association between the change of the central CX3CL1 and the change of the central inflammatory factor is detected.3.By comparing the activation number of central microglia cells in hippocampus,and the changes of inflammatory cytokines TNF-β,IL-1 β,CX3CL1 before and after operation,and CX3CR1 receptor in cerebrospinal fluid and hippocampus,we could illustrate whether CX3CL1 affect the occurrence of POCD by CX3CL1 acting on CX3CR1 receptors on microglia cells to regulate the microglia releasing of inflammatory factors.Methods: Part 1: To establish a model of tibial fracture,16 male SD rats were randomly divided into the model group and the control group,and the changes in behavioral indexes,central inflammatory factors and CX3CL1 expression of the rats in the two groups were measured on the 1st to 5th day after the operation of tibial fracture.Part 2: sixteen male SD rats were randomly divided into the model group and the control group.The number of microglial cells activated and the expression of CX3CR1 receptor on the hippocampal area of the rats in the two groups were measured at 6 hours and 24 hours after surgery respectively.Results: 1.2 to 5 days after modeling,the sailing time and distance of the water maze experiment in the tibial fracture group were significantly longer than those in the control group(P < 0.05),which proved that the model of cognitive dysfunction in the model group was successful.2.On the third day after operation,levels of the inflammatory factors TNF-β and IL-1-β in the serum of the model group were higher than those in the control group,while the concentration of chemokine CX3CL1 was lower than that in the control group(P < 0.05).The expression of inflammatory factor TNF-β and IL-1 β in hippocampus in rats was higher than that in control group,while the expression of chemokine CX3CL1 was less than that in control group(P < 0.05).The concentration of TNF-β and IL-1 β in cerebrospinal fluid of rats was higher than that in control group,while the concentration of chemokine CX3CL1 was lower than that in control group(P < 0.05).3.At 6h,24 h after modeling,the number of microglial cell activation in the hippocampus of the tibial fracture group was significantly higher than that of the control group,while the expression of CX3CR1 receptor on the cell surface was lower than that of the control group(P < 0.05).It suggested that the increase in the number of activation microglial cell in the hippocampal area after surgery in rats was associated with the occurrence of POCD in ratst,and the decreased expression of CX3CR1 receptor on the cell surface might be associated with the increase in the number of activation microglial cell.Conclusions: 1.It’ suggests that the concentration of inflammatory factor in serum was increased,the expression of inflammatory factor in hippocampus increased,the concentration of inflammatory factor in cerebrospinal fluid was increased,while the concentration and the expression of chemokine CX3CL1 was decreased,were associated with the occurrence of POCD in rats.2.Data showed that the occurrence of POCD in rats was related to the increase in the number of activated microglia cells in the central hippocampus.The expression of CX3CR1 receptor on the surface of activated microglia cells was decreased.Whether the CX3CL1 regulates the occurrence of POCD by CX3CL1 acting on CX3CR1 receptors to regulate microglia,and requires further experiments to confirm.Part II The effect of dexmedetomidine on the postoperative of dysfunction induced by tibia fracture surgery of ratsBackground: Dexmedetomidine is a novel high-efficiency,high-selectivity,a 2-adrenalin receptor agonist,which has the effects of sedative,analgesic and anti sympathetic,inhibiting the post-operative stress reaction and inflammatory reaction of the body,and does not inhibit the respiratory function.At present,it is widely used in the field of intensive care and clinical anesthesia.In recent years,more and more studies have shown that dexmedetomidine can improve postoperative cognitive function in elderly patients and reduce the incidence of POCD in patients,but its mechanism of action is still unclear.The occurrence of POCD is related to the central inflammatory response,and the chemokine CX3CL1 has a regulatory effect on the central inflammatory response.Our previous experiments also confirmed that the change of CX3CL1 in the central nervous system of rats is correlated with the change of central inflammatory factors and the occurrence of POCD.Regulating the central inflammatory response through the regulation of chemokine CX3CL1 may be a mechanism for the treatment and remission of POCD.It is not clear whether Dexmedetomidine plays an important role in the remission and intervention of POCD.In order to clear the effect of Dexmedetomidine preconditioning on cognitive dysfunction and the relationship between Dexmedetomidine and CX3CL1,we established the model of tibial fracture after operation in rats.Objective: 1.To study the behavioral indicators of the rats by establishing the POCD model,and to evaluate the cognitive function of the rats by using the Y-maze to determine the changes of cognitive behavior before and after the fracture of the tibia.2.To clear the expression of the CX3CL1 protein and the expression of the CX3CL1 m RNA in the hippocampus correlated with the occurrence of POCD in the rats.3.To study the effect of dexmedetomidine on the cognitive function by tibial fracturesurgery in rats and its relationship with the expression of the central CX3CL1 proteinand the CX3CL1 m RNA.Methods: The first stage: 16 male rats were randomly divided into control group and tibia fracture group.On the 1st,3rd,5th,7th day after operation,the behavioral indexes and the expression of CX3CL1 protein and CX3CL1 m RNA in hippocampus of the two groups were measured.The second stage: 24 male SD rats were randomly divided into three groups: control group,tibial fracture group and CX3CL1 neutralizing antibody group.The changes in the behavioral indexes and the expression of CX3CL1 protein in hippocampus of rats in each group were measured respectively.The third stage: 24 male SD rats were randomly divided into three groups: control group,tibial fracture group and tibial fracture +Dexgroup.The changes in the behavioral indexes and the expression of CX3CL1 protein and CX3CL1 m RNA in hippocampus of rats in each group were measured respectively.Results:1.On the 1st,3rd,5th,7th day after the establishment of the model,the exploration time of the new hetero-arm in the tibial fracture group was significantly shorter than that in the control group(P<0.05).The expression of CX3CL1 protein and CX3CL1 m RNA in the hippocampus of the tibial fracture group was significantly lower than that of the control group(P<0.05).2.The exploration time of the new hetero-arm in the tibia fracture+CX3CL1 neutralizing antibody group was significantly shorter than that of the tibial fracture group(P<0.05).The expression of CX3CL1 protein in hippocampus in the tibia fracture +CX3CL1 neutralizing antibody group was significantly lower than that of tibial fracture group(P<0.05).3.The exploration time of the new hetero-arm in the Dex group was significantly longer than that of the tibial fracture group(P<0.05).The expression of the CX3CL1 protein and the CX3CL1 m RNA in the hippocampus of the Dex group was significantly higher than that of the tibial fracture group(P<0.05).Conclusion: 1.Under this experiment condition,the occurrence of POCD is related to the inflammatory response of the central nervous system.The increased expression of chemokine CX3CL1 in the central nervous system can reduce the release of central inflammatory factors releasing and improve the occurrence of POCD.2.The results suggest that Dexmedetomidine pretreatment can decrease the occurrence of POCD,by increasing the expression of CX3CL1 in the central hippocampus of rats and thus improve the cognitive dysfunction after operation.