TLR4信号对睡眠剥夺诱导小鼠抑郁症中的作用  

The effect of TLR4 signal on paradoxical sleep deprivation-induced depression in mice

作　　者：张丞[1] 唐潇潇 胡曼娜[1] 阿地拉·阿吉 Zhang Cheng;Tang Xiaoxiao;Hu Manna;Adila·Aji(Department of Clinical Psychology,People's Hospital of Xinjiang Uygur Autonomous Region,Xinjiang 830001,China)

机构地区：[1]新疆维吾尔自治区人民医院临床心理科,乌鲁木齐830001

出　　处：《脑与神经疾病杂志》2023年第1期1-7,共7页Journal of Brain and Nervous Diseases

基　　金：新疆维吾尔自治区人民医院科技引进创新项目(20180212);新疆维吾尔自治区自然科学基金项目(2018D01C122)。

摘　　要：目的探究TLR4蛋白对长期异相睡眠剥夺(PSD)诱导抑郁样行为小鼠脑组织中炎症反应的影响。方法45只小鼠随机分为对照(Control)组、模型(Model)组与NLRP3抑制剂(TAK242)组。取Model与TAK242组小鼠,将小鼠放置在水上平台剥夺异相睡眠期,连续5d,期间TAK242组小鼠连续腹腔注射10 mg·kg-1TAK242溶液。取各组小鼠开展糖水偏好测试、悬尾测试、强迫游泳测试与社交互动测试,取小鼠脑脊液检测炎性细胞因子释放,取全脑组织进行免疫荧光染色,取海马体开展PCR定量分析与Western blotting。结果与Control组相比,Model组小鼠糖水摄取率明显减少,强迫游泳、悬尾不动时间增加,社交互动时间减少(P<0.05)。此外,Model组小鼠TLR4 mRNA水平,Iba1荧光表达,炎性细胞因子含量,p-NF-κB与NLRP3表达明显增加(P<0.05)。与Model组相比,TAK242组小鼠糖水摄取率明显增加,强迫游泳、悬尾不动时间减少,且社交互动时间增加(P<0.05)。此外,TAK242组小鼠TLR4 mRNA水平,Iba1荧光表达,炎性细胞因子含量,且p-NF-κB与NLRP3表达明显减少(P<0.05)。线性分析显示,TLR4mRNA表达与小鼠糖水摄取率高度相关,与强迫游泳、悬尾不动时间,社交互动时间中度相关,与炎性细胞因子含量高度相关。结论TLR4表达与长期PSD诱导小鼠抑郁样行为明显相关,通过抑制TLR4蛋白表达能够明显减少炎性细胞因子释放,改善小鼠抑郁症状。Objective To explore the effect of TLR4 protein on the inflammatory response in the brain of mice with long-term paradoxical sleep deprivation(PSD)-induced depression-like behavior.Methods 45 mice were randomly divided into Control group,Model group and NLRP3 inhibitor(TAK242)group.Put the mice of Model and TAK242 groups on the platforms over water for paradoxical sleep deprivation for 5d,during which the mice in the TAK242group are continuously administrated with 10 mg·kg-1TAK242.Then,sucrose preference test,tail suspension test,forced swimming test and social interaction test were carried out to evaluate depression-like behavior,cerebrospinal fluid was used to detect inflammatory cytokine release,the whole brains were taken for immunofluorescence staining,and hippocampus tissues were picked out for PCR quantitative analysis and Western blotting.Results Compared with Control group,the sucrose preference percentage of the mice in Model group significantly reduced,the immobility time of forced swimming and tail suspension increased,and the time of social interaction reduced(P<0.05).In addition,the level of TLR4mRNA,Iba1 immunofluorescence,inflammatory cytokines,as well as p-NF-κB and NLRP3 expression significantly increased in the mice of Model group(P<0.05).Compared with Model group,the sucrose preference percentage of the mice in TAK242 group significantly increased,the immobility time of forced swimming and tail suspension reduced,and the time of social interaction increased(P<0.05).In addition,the level of TLR4 mRNA in the TAK242 group significantly reduced,and Ibal immunofluorescence,inflammatory cytokines,and p-NF-K B and NLRP3 expression significantly decreased in the mice of TAK242 group(P<0.05).Linear analysis showed that the expression of TLR4 mRNA was highly correlated with the sucrose preference percentage of mice,moderately correlated with forced swimming and suspension immobility time,and social interaction time,and highly correlated with the content of inflammatory cytokines.Conclusion TLR4 expres

关 键 词：TOLL样受体-4 异相睡眠剥夺 抑郁症 炎性细胞因子 线性相关 

分 类 号：R741[医药卫生—神经病学与精神病学]