SAA1通过促进小胶质细胞活化影响麻醉术后老年小鼠谵妄样行为  

SAA1 Affects Delirium-like Behavior in Aged Mice after Anesthesia by Promoting Microglial Activation

作　　者：刘君 先元晖 李家辉 吴燕[1] 裴慧慧 高宇博[1] LIU Jun;XIAN Yuanhui;LI Jiahui;WU Yan;PEI Huihui;GAO Yubo(Department of Anesthesiology and Perioperative Medicine,General Hospital of Ningxia Medical University,First Clinical Medical College of Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学总医院麻醉与围术期医学科,宁夏医科大学第一临床医学院,银川750004

出　　处：《宁夏医科大学学报》2025年第2期116-124,134,共10页Journal of Ningxia Medical University

基　　金：宁夏自然科学基金项目(2024AAC03547;2023AAC03652)。

摘　　要：目的探究老年小鼠脑内海马区血清淀粉样蛋白A1(SAA1)表达对麻醉手术后小鼠谵妄样行为的影响。方法将36只18月龄C57BL/6J小鼠随机分为正常对照组(C组)、麻醉/手术组(A/S组)、正常老年小鼠+SAA1抑制剂组(C+SGA360组)和麻醉/手术老年小鼠+SAA1抑制剂组(A/S+SGA360组)。对C组、A/S组小鼠应用旷场实验、觅食实验检测小鼠谵妄样行为,应用Western blot、RT-qPCR检测小鼠脑内海马SAA1蛋白和mRNA表达量,应用免疫荧光检测小胶质细胞形态数量变化。麻醉术前3 d给予C+SGA360组、A/S+SGA360组腹腔注射20mg·kg^(-1) SAA1抑制剂SGA360,每天1次,麻醉术后24 h对各组小鼠进行谵妄样行为(旷场实验、觅食实验)观察并提取脑组织,RT-qPCR检测海马组织中SAA1和Iba1的mRNA表达,检测促炎因子白细胞介素(interleukin,IL)-1β、IL-6和肿瘤坏死因子(tumor necrosis factor,TNF)-α以及CD86 mRNA表达变化,免疫荧光检测小鼠海马区SAA1、Iba1和CD86的荧光表达分布,并观察小胶质细胞的形态变化。结果与C组相比,A/S组老年小鼠表现出明显的谵妄样行为,SAA1蛋白表达水平上调,SAA1、Iba1、CD86及促炎因子IL-1β、IL-6、TNF-α的mRNA表达水平升高,SAA1、CD86荧光表达量增加,小胶质细胞数量增加、胞体增大、突起分枝减少(P均<0.05)。与A/S组相比,A/S+SGA360组小鼠谵妄样行为明显改善,SAA1、Iba1、CD86及促炎因子IL-1β、IL-6、TNF-αmRNA表达水平降低,SAA1、CD86荧光表达量减少,小胶质细胞数量减少、胞体减小、突起分枝增多(P均<0.05)。结论麻醉手术后,老年小鼠脑内SAA1表达升高,可能促进小胶质细胞活化和神经炎症,引发小鼠谵妄样行为。Objective To investigate the effect of SAA1 expression in hippocampus of old mice on delirious-like behavior after anesthesia operation.Methods 3618-month-old C57BL/6J mice were randomly divided into a normal control group(C group,12 mice),an anesthesia/surgery group(A/S group,12 mice),a normal elderly mouse+SAA1 inhibitor group(C+SGA360 group,6 mice),and an anesthesia/surgery elderly mouse+SAA1 inhibitor group(A/S+SGA360 group,6 mice).The open field experiment and foraging experiment were used to detect delirium-like behavior in mice in groups C and A/S.Western blot and RT qPCR were used to detect the expression levels of SAA1 protein and mRNA in the hippocampus of mice,and immunofluorescence was used to detect changes in the morphology and quantity of microglia.Subsequently,the C+SGA360 group and the A/S+SGA360 group were intraperitoneally injected with SAA1 inhibitor SGA36020 mg·kg^(-1) three days before anesthesia surgery,once a day.24 h after anesthesia surgery,delirium-like behavior was detected in each group of mice(open field experiment,foraging experiment),and brain tissue was extracted.RT qPCR was used to detect the mRNA expression of SAA1 and Iba1 in hippocampal tissue,and the expression changes of pro-inflammatory factors IL-1β,IL-6,TNF-α,and CD86 mRNA were detected.Immunofluorescence was used to detect the fluorescence expression distribution of SAA1,Iba1,and CD86 in the mouse hippocampus,and the morphological changes of microglia were observed.Results Compared with group C,the elderly mice in group A/S showed obvious delirium-like behavior,the expression level of SAA1 protein was upregulated,the mRNA expression levels of SAA1,Iba1,CD86 and pro-inflammatory factors IL-1β,IL-6 and TNF-α were increased,and the fluorescence expressions of SAA1 and CD86 were increased.The number of microglia increased,the cell body enlarged and the protrusion branches decreased(P<0.05).Compared with A/S group,delirious behavior of mice in A/S+SGA360 group was significantly improved,mRNA expression levels of SAA1,Iba

关 键 词：术后谵妄 血清淀粉样蛋白A1 小胶质细胞活化 老年小鼠 

分 类 号：R749.1[医药卫生—神经病学与精神病学]