咖啡因对睡眠剥夺模型大鼠脑电和免疫系统功能的影响  

Effect of caffeine on brain electrical changes and immune responses in sleep-deprived model rats

作　　者：王川 高荣[3] 房鑫鑫 常海霞 李云峰 王恒林 张黎明[3] WANG Chuan;GAO Rong;FANG Xin-xin;CHANG Hai-xia;LI Yun-feng;WANG Heng-lin;ZHANG Li-ming(Graduate School of Hebei North Institute,Zhangjiakou 075000,China;Department of anesthesiology,the 8th Medical Center of Chinese PLA General Hospital,Beijing 100094,China;State Key Laboratory of Toxicology and Medical Countermeasures,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China;Institute of Military Cognitive and Brain Sciences,Academy of Military Medical Sciences,Beijing 100850,China)

机构地区：[1]河北北方学院研究生院,河北张家口075000 [2]解放军总医院第八医学中心麻醉科,北京100094 [3]军事科学院军事医学研究院毒物药物研究所,抗毒药物与毒理学国家重点实验室,北京100850 [4]军事科学院军事医学研究院军事认知与脑科学研究所,北京100850

出　　处：《中国药理学与毒理学杂志》2022年第6期435-442,共8页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金(81773708)。

摘　　要：目的研究咖啡因(CAF)对睡眠剥夺(SD)模型大鼠睡眠时相、γ振荡和免疫系统功能的影响。方法Wistar大鼠分为正常对照组、SD组和SD+CAF组。除正常对照组外,其余各组利用跑台式睡眠剥夺仪建立大鼠72 h SD模型,建模同时SD+CAF组大鼠ig给予CAF 50 mg·kg^(-1)(连续4 d,每天1次)。大鼠于建模前、后分别连续记录肌电和脑电信号,分析末次给药后4 h内大鼠睡眠时相和γ振荡功率谱密度;ELISA检测大鼠脾、海马和前额叶皮质(PFC)白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)和IL-10含量;Western印迹法检测大鼠脾组织Toll样受体4(TLR 4)和NF-κB蛋白表达水平;免疫荧光染色检测海马和内侧前额叶皮质(mPFC)活化的小胶质细胞数量。结果与正常对照组相比,SD组大鼠每小时觉醒时间(P<0.05)和总觉醒时间(P<0.01)缩短,每小时非快眼动睡眠时间(P<0.05)、总非快眼动睡眠时间(P<0.01)和总快眼动睡眠时间(P<0.05)延长,γ振荡在43~62 Hz频段振荡功率谱密度降低(P<0.05);脾和海马组织中IL-1β和TNF-α含量增高(脾:P<0.05,海马:P<0.01),IL-10含量降低(P<0.01);PFC组织中IL-1β含量升高(P<0.01),IL-10含量降低(P<0.05);脾组织TLR4(P<0.05)和NF-κB(P<0.01)蛋白表达水平增高;海马齿状回和mPFC中活化的小胶质细胞数量增多(P<0.01)。CAF 50 mg·kg^(-1)可逆转上述变化。结论CAF可调节SD模型大鼠的睡眠结构和γ振荡、抑制小胶质细胞功能及中枢和外周炎症反应。OBJECTIVE To study the effect of caffeine(CAF) on the sleep phase, gamma oscillations and immune system function in sleep deprivation(SD) model rats. METHODS Rats were divided into the normal control group, SD group and SD+CAF group. Except for the normal control group, a 72 h SD model was established using a treadmill sleep deprivation apparatus in the other two groups. At the same time, rats in the SD+CAF group were ig given CAF 50 mg·kg-1(for four consecutive days, once a day). The signals of electroencephalograms and electromyography of rats were continuously recorded before and after modeling, and the sleep phase and gamma oscillation intensity within 4 h of the last administration were analyzed. ELISA was used to detect the levels of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α) and IL-10 in the spleen, hippocampus and prefrontal cortex(PFC) of rats. Western blotting was used to detect the protein expression levels of Toll-like receptor 4(TLR 4) and NF-κB, while immunofluorescence staining was used to detect the number of activated microglia in the hippocampus and medial prefrontal cortex(mPFC). RESULTS Compared with the normal control group, rats in the SD group had shorter wake time per hour(P<0.05) and total wake time(P<0.01), while non-rapid eye movement(NREM) sleep time per hour(P<0.05), total NREM sleep time(P<0.01) and total REM sleep time(P<0.05) were prolonged. In the SD group, the power spectral density of oscillations was decreased at the frequency of 43-62 Hz(P<0.05). The contents of IL-1β and TNF-α in the spleen and hippocampus were significantly increased(spleen: P<0.05, hippocampus: P<0.01), while the content of IL-10 was decreased(spleen: P<0.01, hippocampus: P<0.01).The content of IL-1β in PFC tissues was increased(P<0.01), while that of IL-10 was decreased(P<0.05). The protein expressions of TLR4(P<0.05) and NF-κB(P<0.01) in spleen tissue were increased,and the number of activated microglia in the dentate gyrus(DG) of the hippocampus and mPFC was increased(P<0.01). CAF 50

关 键 词：睡眠剥夺 咖啡因 认知障碍 γ振荡 炎症 

分 类 号：R964[医药卫生—药理学] R967[医药卫生—药学]