中国病理生理杂志2026,Vol.42Issue(3):468-476,9.DOI:10.3969/j.issn.1000-4718.2026.03.006
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
Effect of normobaric oxygen therapy on depression-like behaviors in mice with chronic fatigue and its immunological mechanisms
摘要
Abstract
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.关键词
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Key words
chronic fatigue/normobaric oxygen/sleep deprivation/chronic restraint stress/neuroinflamma-tion/NLRP3 inflammasome分类
医药卫生引用本文复制引用
李子璇,张世博,张赟恺,刘蕊桑,侯登勇,蔡淑淇,任小孟..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[J].中国病理生理杂志,2026,42(3):468-476,9.基金项目
国家自然科学基金青年基金项目(No.32400727) (No.32400727)
上海市自然科学基金面上项目(No.24ZR1481100) (No.24ZR1481100)