| ObjectiveTo explore the role and possible mechanism of Glatiramer acetate(GA)in postoperative cognitive dysfunction in elderly mice,and provide new ideas for clinical prevention and treatment of POCD.MethodsA total of 60 male C57BL/6J mice(11 months)weighing 28-32?g were included in the present study.Using a random number table,60 mice were divided into the following three groups: control group(group C),operation group(group S),drug group(group GA),with 20 mice in each group.Group C:mice underwent a sham procedure;Group S and Group GA: mice underwent underwent abdominal surgery.Three groups of elderly mice were injected once a day for a total of 4 times from one day before operation to the second day after operation.Group GA: GA 200ug+0.01 M PBS 200 μ l,subcutaneous injection.Group C and Group S were subcutaneously injected with the same volume of PBS.The following tests were performed after operation:(1)Morris water maze test was used to detect the changes of cognitive function in aged mice.(2)the levels of serum inflammatory cytokines IL-1 β and IL-6 were detected by ELISA.(3)Immunofluorescence staining was used to detect the activation of microglia and the morphological changes of Claudin-1 in choroid plexus(CP)epithelium 3 days after operation.(4)the gene expression of ICAM-1 and CCL2 in choroid plexus was detected by real-time quantitative PCR.Results1.Morris water maze experiment.(1)Positioning navigation experiment.Compared with Group C,there was no significant difference in escape latency between Group S and Group C(P > 0.05).In Group GA,the escape latency was significantly shortened at 21 days(T21)after operation,but there was no significant difference at other time points(P > 0.05).(2)Space exploration experiment.Compared with group C,the length of stay in the target quadrant and the number of times crossing the platform in group S were significantly decreased at 14 days(T14)after operation,and there was significant difference(P < 0.05),but there was no significant difference at other time points(P > 0.05).The length of stay in the target quadrant of the aged mice in the Group GA had no significant difference at each time point,but compared with the Group S,the length of stay in the target quadrant and the times of crossing the platform of the aged mice in the Group GA were significantly increased at T14 time point,and there was no significant difference at other time points.2.ELISA detection.The results of serum inflammatory factors 3 days after operation showed that the levels of IL-1 β and IL-6 in Group S were significantly higher than those in group C,while IL-1 β and IL-6 in Group GA were significantly lower than those in Group S(P < 0 05).The results showed that the levels of serum inflammatory factors in Group S were significantly higher than those in Group C(P < 0 05),IL-1 β and IL-6 in Group GA were significantly lower than those in Group S.3.Pathological changes of brain tissue.(1)Activation of microglia in hippocampus.Compared with Group C,the number of activated microglia in Group S increased(P <0.05),the cell body enlarged and the processes became shorter.There was no significant increase in activated microglia and no obvious morphological changes in Group GA.(2)Histological changes of choroid plexus.The expression of Claudin-1 in LVCP epithelial cells of choroid plexus of lateral ventricle in three groups of aged mice was compared under fluorescence microscope 3 days after operation.Claudin-1 showed a typical honeycomb immune response pattern.LVCP: compared with Group C,the cellular immune response of Claudin-1 on CP in Group S was interrupted and weakened.In Group GA,the Claudin-1 cellular immune response of CP was intact and weakened.4.Real-time quantitative PCRThe expressions of ICAM-1 and CCL2 genes in the ventricular choroid plexus of the three groups were compared on the T3 after operation.The results of PCR showed that the expression of ICAM-1 in Group S was significantly lower than that in Group C,and the expression of CCL2 in Group S was significantly higher than that in Group C and Group GA.Conclusions1.GA alleviated the neuroinflammation in elderly mice after abdominal surgery,thus reduced the occurrence of POCD.2.GA reduced the incidence of cognitive impairment after abdominal surgery in elderly mice by regulating the immune mechanism of ventricular choroid plexus.It was found that the imbalance of choroid plexus immune function would lead to the occurrence of POCD. |
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