小胶质细胞极化探讨Sev对SD诱发大鼠抑郁样症状与认知功能障碍的影响  

Effects of sevoflurane on sleep deprivation-induced depression-like symptoms and cognitive dysfunction in rats based onmicroglia polarization

作　　者：王健[1] 葛树胜 Wang Jian;Ge Shusheng(Department of Anesthesiology,the First Affiliated Hospital of Hainan Medical College,Haikou 570102,China)

机构地区：[1]海南医学院第一附属医院麻醉科,海口570102

出　　处：《脑与神经疾病杂志》2023年第8期511-516,共6页Journal of Brain and Nervous Diseases

基　　金：海南省卫生健康行业科研项目(21A200011)。

摘　　要：目的 探讨七氟醚(Sev)对睡眠剥夺(SD)诱发大鼠抑郁样症状与认知功能障碍的调控作用,明确小胶质细胞的影响。方法 48只SD大鼠随机分为对照(Con)组、睡眠剥夺(SD)组、SD+1%Sev (SD+1%Sev)组、SD+3%Sev (SD+3%Sev)组,每组12只。模型构建前开展Morris水迷宫与糖水偏好训练。取SD组大鼠进行48h SD模型构建,通过1%或3%Sev治疗后开始Morris水迷宫与糖水偏好测试。处死大鼠后取脑组织用于ELISA检测下丘脑-垂体-肾上腺轴相关细胞因子含量,免疫荧光检测离子钙结合接头分子1 (iba1)表达,实时荧光定量PCR检测M1/M2型小胶质细胞标记物mRNA表达。结果 与Con组相比,SD组大鼠首次达到平台时间增加,穿越平台次数减少,第Ⅲ象限停留时间减少,糖水偏好摄取率降低;与SD组相比,SD+1%Sev组大鼠首次达到平台时间减少,穿越平台次数与第Ⅲ象限停留时间增加,糖水偏好摄取率提高;然而,3%Sev+SD组大鼠这些指标没有明显变化。与此同时,与Con组相比,SD组大鼠iba1平均荧光强度增加;与SD组相比,SD+1%Sev组iba1平均荧光强度降低。此外,与Con组相比,SD组CD16、肿瘤细胞坏死因子-α (TNF-α)、白介素-1β (IL-1β)、一氧化氮合成酶(iNOS) mRNA表达增加;与SD组相比,SD+1%Sev组CD16、TNF-α、IL-1β、iNOS mRNA表达减少,且CD206、转化生长因子-β (TGF-β)、精氨酸酶1 (Arg1)、几丁质酶样蛋白1 (Ym1) mRNA表达增加。结论 1%Sev通过抑制小胶质细胞促炎表型极化,提高抗炎表型极化,减轻SD诱导的抑郁样症状与认知功能障碍。Objective To investigate the effect of sevoflurane(Sev)on sleep deprivation(SD)-induced depressive-like symptoms and cognitive dysfunction in rats,and to clarify the effect of microglia.Methods 48 SD rats were randomly divided into control(Con)group,SD group,SD+1%Sev(SD+1%Sev)group,SD+3%Sev(SD+3%Sev)group,12 animals in each group.Morris water maze and sucrose preference training were arranged before the model constructed.Rats in SD group experienced a 48-h SD for model construction.Morris water maze and sucrose preference test were started after treatment with 1%or 3%Sev.Then,the rats were sacrificed,the brains were collected for detection of hypothalamic-pituitary-adrenal axis related cytokines by ELISA.As well as the expression of ibal was detected by immunofluorescence,and the mRNA expression of M1/M2 type microglia marker were detected by RT-PCR.Results Compared with Con group,the rats in SD group increased the first arrival time to the platform,decreased the number of platform crossing and the resident time in the III quadrant,and decreased the sucrose preference.Compared with SD group,the first arrival time to the platform of the rats in SD+1%Sev group deceresed,t the number of platform crossing and the resident time in the II quadrant increased,and the sucrose preference increased.However,these indicators did not change significantly in the 3%Sev+SD group.At the same time,compared with Con group,the MFI of ibal in the SD group increased;compared with SD group,the MFI of ibal in the SD+1%Sev group decreased.In addition,compared with Con group,the expression of CD16,TNF-α,IL-1β,iNOS mRNA in SD group increased;compared with SD group,the expression of CD16,TNF-α,IL-1β,iNOS mRNA in SD+1%Sev group decreased,and the expression of CD206,TGF-β,Arg1,Ym1 mRNA increased.Conclusion 1%Sev can reduce the depressive-like symptoms and cognitive dysfunction induced by SD through inhibiting the pro-inflammatory phenotype polarization of microglia and increasing the anti-inflammatory phenotype polarization.

关 键 词：七氟醚 睡眠剥夺 小胶质细胞 炎症反应 剂量 

分 类 号：R749[医药卫生—神经病学与精神病学]