片段化睡眠对术后认知功能和中枢神经炎症的影响

Effect of fragmented sleep on postoperative cognitive function and central neuroinflammation

目的以老龄小鼠片段化睡眠(SF)模型模拟临床术后患者的睡眠模式,探讨术后片段化睡眠对围术期神经认知障碍(PND)和中枢神经炎症的影响。方法32只老龄ICR小鼠随机分为4组(n=8):正常组(C组)、手术组(S组)、片段化睡眠组(F组)和手术+片段化睡眠组(D组)。于胫骨骨折内固定手术后进行片段化睡眠干预,采用新物体识别实验和条件性恐惧实验进行认知功能评估,采用ELISA检测海马炎症因子表达的变化。结果新物体识别实验:C组、S组、F组和D组小鼠辨别指数(RI)分别为0.69±0.07、0.48±0.07、0.54±0.10、0.50±0.12,S组、F组和D组小鼠RI均显著低于C组(t=4.885、3.521、4.433,均P<0.01),S组和D组小鼠RI差异无统计学意义(t=0.9671,P>0.05)。场景恐惧实验:C组、S组、F组和D组小鼠僵直时间分别为(21.34±6.48)、(13.83±4.26)、(11.50±6.25)、(6.17±4.77)s,S组、F组和D组小鼠僵直时间均显著低于C组(t=2.722、3.566、5.496,P<0.05或P<0.01),D组小鼠僵直时间显著低于S组(t=2.774,P<0.05)。线索恐惧实验:C组、S组、F组和D组小鼠僵直时间分别为(74.36±17.09)、(43.91±9.71)、(46.34±13.43)、(24.90±14.21)s,S组、F组和D组小鼠僵直时间均显著低于C组(t=4.393、4.043、7.136,均P<0.01),D组小鼠僵直时间显著低于S组(t=2.743,P<0.05)。S组、F组和D组小鼠海马肿瘤坏死因子(TNF-α)、白细胞介素(IL)-6和IL-1β均显著高于C组,D组小鼠海马TNF-α、IL-6显著高于S组,差异均有统计学意义(P<0.05或P<0.01)。结论术后片段化睡眠加剧老龄小鼠术后认知功能损害,增加海马炎症因子的表达。

Objective To investigate the effect of sleep fragmentation on perioperative neurocognitive disorders(PND)and central neuroinflammation by simulating sleep patterns of postoperative patients with sleep fragmentation in aged mice.Methods Thirty-two elderly ICR mice were randomly divided into four groups(n=8):normal group(C),surgery group(S),fragmented sleep group(F),and surgery+fragmented sleep group(D).Fragmented sleep was conducted after internal fixation of tibia fractures,cognitive function was evaluated by novel object recognition(NOR)and fear conditioning(FC)test,and changes in expression of inflammatory cytokines in hippocampus were detected by ELISA.Results NOR test:the recognition index(RI)of mice in group C,group S,group F and group D was 0.69±0.07,0.48±0.07,0.54±0.10 and 0.50±0.12,respectively.The RI of mice in group S,group F and group D was significantly lower than that in group C(t=4.885,3.521 and 4.433,all P<0.01).There was no significant difference in RI between group S and group D(t=0.9671,P>0.05).Contextual FC test:the freezing time of mice in group C,group S,group F and group D was(21.34±6.48),(13.83±4.26),(11.50±6.25)and(6.17±4.77)s,respectively.The freezing time of mice in group S,group F and group D was significantly lower than that in group C(t=2.722,3.566,5.496,P<0.05 or P<0.01).The freezing time of mice in group D was significantly lower than that in group S(t=2.774,P<0.05).Cue FC test:the freezing time of mice in group C,group S,group F and group D was(74.36±17.09),(43.91±9.71),(46.34±13.43)and(24.90±14.21)s,respectively.The freezing time of mice in group S,group F and group D was significantly lower than that in group C(t=4.393,4.043 and 7.136,all P<0.01).The freezing time of mice in group D was significantly lower than that in group S(t=2.743,P<0.05).The levels of TNF-α,IL-6 and IL-1βin hippocampus of mice in group S,F and D were significantly higher than those in group C,while the levels of TNF-αand IL-6 in hippocampus of mice in group D were significantly higher than those in group S,with statistically significant differences(P<0.05 or P<0.01).Conclusion Postoperative fragmented sleep aggravates postoperative cognitive impairment and increases the hippocampal neuroinflammation in aged mice.