常压氧疗对慢性疲劳小鼠抑郁样行为的作用及其免疫机制研究OA
Effect of normobaric oxygen therapy on depression-like behaviors in mice with chronic fatigue and its immunological mechanisms
目的:通过构建模拟人类长期职业性作业疲劳的小鼠模型,观察慢性疲劳对小鼠中枢神经系统和行为改变的影响,探究常压氧疗缓解慢性疲劳相关神经炎症和抑郁状态的作用及免疫学机制.方法:将小鼠随机分成对照(control)组、常压氧疗(30%O2)组、慢性疲劳模型(model)组和治疗组(包括model+30%O2-0.5 h组、model+30%O2-1.5 h组和model+30%O2-6 h组).对model组和3个治疗组进行持续4周的18 h睡眠剥夺和2 h慢性束缚应激,以建立慢性疲劳小鼠模型.治疗组在模型建立期间分别接受不同时长的30%O2环境干预治疗,持续4周.统计小鼠的体重变化率以评估小鼠生理状态;采用旷场实验和高架十字迷宫实验评估各组小鼠的抑郁水平;测定小鼠海马白细胞介素1β(interleukin-1β,IL-1β)、IL-6、IL-18和肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)水平以评估小鼠神经炎症水平;利用双皮质醇和离子钙结合适配器分子1免疫荧光染色观察小鼠下丘脑神经发生和小胶质细胞活化情况;通过免疫荧光染色和Western blot评估常压氧疗对慢性疲劳小鼠下丘脑核苷酸结合寡聚化结构域样受体蛋白3(nucleotide-binding oligomerization domain-like receptor protein 3,NLRP3)炎症小体活化的调节作用.结果:从模型建立第9天开始,control组与model组小鼠的体重变化率即表现出显著差异,且差异在造模期间持续存在,表明慢性疲劳小鼠模型的成功构建;行为学结果显示,model组小鼠表现出抑郁样行为,同时海马组织中IL-1β、IL-6、IL-18和TNF-α水平升高,表明慢性疲劳可触发神经炎症;30%O2干预0.5和1.5 h组小鼠在旷场实验中心区域停留时间及进入高架十字迷宫开臂次数的百分比均显著增加;免疫荧光和Western blot结果均显示1.5 h组小鼠下丘脑NLRP3蛋白表达及炎症小体活化水平降低,提示该时长的常压氧疗能够缓解NLRP3相关神经炎症.结论:常压氧疗能有效减轻慢性疲劳相关神经炎症和抑郁样行为,其机制与调控中枢神经系统中NLRP3炎症小体活化有关.
AIM:Utilizing a mouse model mimicking human chronic occupational fatigue,this study investi-gated the effects of chronic fatigue on the central nervous system and behaviors,and the therapeutic potential and immuno-logical mechanisms of normobaric oxygen therapy in mitigating fatigue-induced neuroinflammation and depression-like be-haviors.METHODS:Mice were randomly divided into 6 groups:control group,normobaric oxygen therapy(30%O2)group,chronic fatigue model group(model group),and 3 treatment groups receiving 30%O2 for 0.5 h(model+30%O2-0.5 h),1.5 h(model+30%O2-1.5 h),and 6 h(model+30%O2-6 h).Chronic fatigue was induced in the model and 3 treatment groups via daily 18-hour sleep deprivation plus 2-hour chronic restraint stress for 4 weeks.Concurrently,the mice in treatment groups received 30%O2 at their respective durations(0.5,1.5,or 6 h daily)for 4 weeks.Physiologi-cal status was monitored via body weight change.Depressive-like behaviors were evaluated using the open-field test(OFT)and elevated plus maze(EPM)test.Hippocampal levels of interleukin-1β(IL-1β),IL-6,IL-18 and tumor necro-sis factor-α were quantified to assess neuroinflammation.Hypothalamic neurogenesis and microglial activation were as-sessed by immunofluorescence staining for doublecortin and ionized calcium-binding adapter molecule-1,respectively.Nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome activation in the hypothalamus was analyzed via immunofluorescence and Western blot.RESULTS:Significant differences in body weight change emerged between the control and model groups starting on day 9 and persisted throughout the experiment.Treatment with 30%O2 for 0.5 or 1.5 h significantly increased the time spent in the central regions in OFT and percentage of open arm en-tries in EPM test.Immunofluorescence and immunoblot analyses demonstrated that normobaric oxygen therapy suppressed both NLRP3 expression and inflammasome activation in the hypothalamus.CONCLUSION:Normobaric oxygen therapy effectively attenuates chronic fatigue-induced neuroinflammation and depression-like behaviors by modulating NLRP3 in-flammasome activation in central nervous system.
李子璇;张世博;张赟恺;刘蕊桑;侯登勇;蔡淑淇;任小孟
上海大学,上海 200444||海军军医大学海军特色医学中心,上海 200433海军军医大学海军特色医学中心,上海 200433||上海海洋大学,上海 201306海军军医大学海军特色医学中心,上海 200433海军军医大学海军特色医学中心,上海 200433海军军医大学海军特色医学中心,上海 200433海军军医大学海军特色医学中心,上海 200433||上海海洋大学,上海 201306海军军医大学海军特色医学中心,上海 200433
医药卫生
慢性疲劳常压氧睡眠剥夺慢性束缚应激神经炎症NLRP3炎症小体
chronic fatiguenormobaric oxygensleep deprivationchronic restraint stressneuroinflamma-tionNLRP3 inflammasome
《中国病理生理杂志》 2026 (3)
468-476,9
国家自然科学基金青年基金项目(No.32400727)上海市自然科学基金面上项目(No.24ZR1481100)
评论