侧脑室注射脂多糖对小鼠海马依赖性空间记忆影响  

Effect of intracerebroventricular injection of lipopolysaccharide on hippocampal-dependent spatial memory in mice

作　　者：刘晓敏[1] 刘俊汝 于明[1] 常雪纯 周宇 王强[1] LIU Xiaomin;LIU Junru;YU Ming;CHANG Xuechun;ZHOU Yu;WANG Qiang(Department of Rehabilitation,The Affiliated Hospital of Qingdao University,Qingdao 266100,China)

机构地区：[1]青岛大学附属医院康复科,山东青岛266100 [2]青岛大学医学部基础医学院生理学与病理生理学系,山东青岛266100

出　　处：《青岛大学学报（医学版）》2024年第5期633-638,共6页Journal of Qingdao University(Medical Sciences)

基　　金：山东省自然科学基金面上项目(ZR2023MH0-51);青岛市自然科学基金原创探索项目(23-2-1-188-zyyd-jch)。

摘　　要：目的探讨脂多糖(LPS)侧脑室注射对小鼠海马依赖性空间记忆的影响。方法(1)将14只3月龄野生型小鼠随机分为对照组(6只)和LPS组(8只),分别侧脑室注射3μL的生理盐水和1 g/L的LPS,随后通过水迷宫实验检测小鼠的空间记忆能力。(2)选10只3月龄野生型小鼠进行水迷宫训练,在第7天空间记忆形成后随机分为对照组和LPS组(每组5只),分别侧脑室注射3μL生理盐水和1 g/L的LPS,并在第9天进行了训练和测试。(3)用1 mg/L的LPS刺激小鼠BV2小胶质细胞,检测促炎症因子肿瘤坏死因子-α(TNF-α)和白细胞介素6(IL-6)的表达。结果水迷宫实验显示,在空间记忆获取训练阶段,LPS组与对照组小鼠找到目标平台的时间差异无显著性,训练时间和药物品种无显著交互效应(F_(交互)=0.712,P=0.6168);在空间记忆形成测试阶段,LPS组在目标象限的探索时间占比与其他象限的差异无显著性(P>0.05);而在记忆形成后侧脑室注射LPS则导致小鼠空间记忆的提取障碍(P<0.05)。LPS组BV2细胞不同处理时间TNF-α和IL-6的mRNA表达均明显上调(P<0.05)。结论海马炎症可导致小鼠空间记忆的获取和提取障碍,其机制可能与小胶质细胞激活有关。Objective To investigate the effect of intracerebroventricular injection of lipopolysaccharide(LPS)on hippocampal-dependent spatial memory in mice.Methods A total of 14 wild-type mice,aged 3 months,were randomly divided into control group with 6 mice and LPS group with 8 mice,and the mice in the control group were given intracerebroventricular injection of 3μL normal saline,while those in the LPS group were given intracerebroventricular injection of 1 g/L LPS.The water maze test was used to observe the spatial memory ability of mice.A total of 10 wild-type mice,aged 3 months,were selected for water maze training and were randomly divided into control group and LPS group after spatial memory formation on day 7,with 5 mice in each group.The mice in the control group were given intracerebroventricular injection of 3μL normal saline,while those in the LPS group were given were given intracerebroventricular injection of 1 g/L LPS,and training and testing were performed on day 9.Mouse BV2 microglial cells were stimulated with 1 mg/L LPS to measure the changes in the inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).Results The water maze test showed that during the training phase for spatial memory acquisition,there was no significant difference in the time spent to find the target platform between the LPS group and the control group,with no significant interaction effect between training time and drug type(F_(interaction)=0.712,P=0.6168);during the test phase for spatial memory formation,the LPS group showed no significant difference in the proportion of exploration time between the target quadrant and the other quadrants(P>0.05);however,after memory formation,intracerebroventricular injection of LPS resulted in impaired retrieval of spatial memory in mice(P<0.05).BV2 cells in the LPS group showed significant increases in the mRNA expression levels of TNF-αand IL-6 at different treatment times(P<0.05).Conclusion Hippocampal inflammation induced by LPS can lead to deficits in both acquisit

关 键 词：空间记忆 神经炎症性疾病 脂多糖类 小神经胶质细胞 海马 小鼠 近交C57BL 

分 类 号：R338.64[医药卫生—人体生理学] R344[医药卫生—基础医学]