声波刺激对慢性睡眠剥夺小鼠认知能力的改善作用及机制研究  

Effects and mechanisms of acoustic wave stimulation on cognitive improvement in chronically sleep-deprived mice

作　　者：高鑫龙 何颖 吴文惠[1] 闵天骄 刘李娜 蒋蓓尔 GAO Xinlong;HE Ying;WU Wenhui;MIN Tianjiao;LIU Lina;JIANG Beier(College of Food Sciences and Technology,Shanghai Ocean University,Shanghai 201306,China;Naval Medical Center,Naval Medical University,Shanghai 200433,China)

机构地区：[1]上海海洋大学食品学院,上海201306 [2]海军军医大学海军特色医学中心,上海200433

出　　处：《军事医学》2025年第2期81-89,共9页Military Medical Sciences

基　　金：国家自然科学基金项目(82173731);军委科技委国防科技应用推进项目。

摘　　要：目的研究声波刺激对睡眠障碍小鼠认知功能的改善作用及机制。方法(1)将36只雄性C57BL/6小鼠随机分为对照组、模型组和声波组,每组12只。通过改良多平台法建立睡眠剥夺小鼠模型,连续剥夺睡眠21 d,每天睡眠剥夺后给与声波组小鼠40 dB/30 min声波刺激治疗;(2)睡眠剥夺期间,记录各组小鼠的一般状态,包括精神状态和体重变化;(3)睡眠剥夺21 d后,依次采用旷场、新物体识别、Y迷宫、Morris水迷宫实验等多种行为学手段观察慢性睡眠剥夺对小鼠自主活动、空间探索能力以及学习记忆等认知功能的影响,并通过免疫组化观察小鼠海马组织中神经元细胞标志物神经元核抗原(NeuN)、星形胶质细胞标志物胶质纤维酸性蛋白(GFAP)、小胶质细胞活化标志物离子化钙结合适配分子1(Iba-1)的阳性表达变化;通过实时定量PCR(qPCR)检测小鼠海马组织中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、诱导型一氧化氮合酶(iNOS)的表达变化;(4)通过转录组测序探究声波刺激改善认知障碍的作用机制。结果睡眠剥夺21 d后,声波刺激显著改善了小鼠的体重下降(P<0.01);声波刺激后小鼠Y迷宫自发交替正确率、新物体识别鉴别指数、Morris水迷宫中小鼠在目标象限停留时间及穿越平台的次数显著增加(P<0.05),逃避潜伏期显著减少(P<0.05);声波刺激后小鼠海马CA3区NeuN平均光密度显著增加(P<0.05)、GFAP、Iba-1免疫阳性细胞数显著减少(P<0.01),海马组织中IL-6、TNF-α、iNOS mRNA表达显著减少(P<0.05)。结论声波刺激可修复神经损伤、调节海马组织炎症反应,改善睡眠剥夺引起的认知缺陷。Objective To study the mechanism by which acoustic wave stimulation improves cognitive function in sleep-deprived mice.Methods(1)Thirty-six male C57BL/6 mice were randomly divided into three groups:the control group,model group and acoustic wave group(n=12 per group).A sleep deprivation model was established using the modified multiple platform method.After 21 days of sleep deprivation in a row,mice in the acoustic wave group were exposed to 30-minute acoustic wave stimulation at 40 dB.(2)During sleep deprivation,the health status of each group of mice was recorded,including the mental state and body weight.(3)After 21 days of sleep deprivation,behavioral tests(open field test,novel object recognition test,Y-maze and Morris water maze)were performed to assess the spontaneous activity,spatial exploration,and such cognitive functions as learning and memory in mice.Immunohistochemistry was conducted to analyze the expressions of neuronal nuclear antigen(NeuN),glial fibrillary acidic protein(GFAP)and ionized calcium-binding adaptor molecule 1(Iba-1)in the hippocampus.Quantitative real-time PCR(qPCR)was used to measure the expression levels of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α)and inducible nitric oxide synthase(iNOS)in the hippocampus.(4)Transcriptome sequencing was employed to explore the mechanism underlying the improvement of cognitive impairment by acoustic wave stimulation.Results After 21 days of sleep deprivation,acoustic wave stimulation significantly alleviated weight loss in mice(P<0.01).The accuracy of Y-maze spontaneous alternation,indexes of novel object discrimination,the time spent in the target quadrant and the number of times the mice crossed the platformin the Morris water maze were all significantly increased(P<0.05),while the escape latency was significantly reduced(P<0.05).The average optical density of NeuN in the hippocampal CA3 region significantly increased(P<0.05),GFAP and Iba-1 immunopositive cell counts significantly decreased(P<0.01),and the mRNA levels of IL-6,TNF-α

关 键 词：睡眠剥夺 声波刺激 神经炎症 认知障碍 小鼠 

分 类 号：R332.8[医药卫生—人体生理学] R741.02[医药卫生—基础医学]