Effect Of Sleep Fragmentation On Cognitive Function In Aged Rats

Objective:To study the effect of sleep fragmentation on postoperative cognitive function in aged rats,to explore the possible pathogenesis of postoperative cognitive dysfunction（POCD）in aged rats,and to provide an effective theoretical basis for the prevention and treatment of POCD.Methods:Eighty clean male SD rats,aged 20-22 months,weighing 500-700 g,were divided into 4 groups by random number table method（n=20）.Normal control group（Control group）,sleep fragmentation group（SF group）,surgical treatment group（Surgery group）,sleep fragmentation+surgery group（SF+Surgery group）.In the SF group,48-hour sleep disturbance was performed on the aged rats by using a sleep disturbance device.The Surgery group underwent tibial fracture internal fixation,and the SF+Surgery group underwent tibial fracture internal fixation after 48 hours of disturbed sleep.From the first day（T₁）to the fifth day（T₅）after surgery,8 rats were randomly selected from each group for Morris water maze test to detect the escape latency and the number of crossing platforms;after the water maze experiment,the rats were sacrificed and taken Hippocampus,brain tissue sections were observed with hematoxylin-eosin staining for changes in neurons of rat hippocampal CA1 region;ELISA was used to measure tumor necrosis factor-α（TNF-α）and white blood cells in rat hippocampus Content of interleukin-6（IL-6）;detection of SOD and MDA levels in the hippocampus by chemical colorimetry;detection of SIRT1,NF-κB,Bax,Caspase-3 protein expression in hippocampal neurons by Western Blot.Results:（1）Compared with the Control group,the SF group,the Surgery group,and the SF+Surgery group have a longer escape latency,fewer crossing platforms,increased levels of TNF-α,IL-6,and MDA,decreased SOD activity,and SIRT1 expression in hippocampal neurons.Decreased,the expression of NF-κB,Bax,and Caspase-3increased,and the spatial learning and memory abilities of rats were significantly reduced（P<0.05）.（2）Compared with the SF group,the escape latency of the SF+Surgery group is longer,the number of crossing platforms is reduced,the levels of TNF-α,IL-6,and MDA are increased,SOD activity is decreased,SIRT1 expression of hippocampal neurons is decreased,and NF-κB,The expression of Bax and Caspase-3 increased,and the rats’spatial learning and memory abilities were significantly reduced（P<0.05）.Except for the decrease of MDA content in the Surgery group（P<0.05）.the other indicators had no significant difference（P>0.05）.（3）Compared with Surgery,the escape latency of SF+Surgery group is longer,the number of crossing platforms is reduced,TNF-α,IL-6,MDA content is increased,SOD activity is reduced,SIRT1 expression of hippocampal neurons is reduced,NF-κB,Bax The expression of Caspase-3 increased,and the spatial learning and memory abilities of rats were significantly reduced（P<0.05）.Conclusion:Sleep fragmentation can lead to postoperative cognitive dysfunction,and its mechanism of action is caused by inhibition of SIRT1,activation of NF-κB,Bax,and Caspase-3,which cause inflammation and oxidative stress in hippocampal neurons.