氟西汀对脓毒症小鼠认知功能的影响

Effect of fluoxetine on cognitive function in septic mice

中文关键词: 氟西汀  脓毒症  认知障碍  神经网络

英文关键词: Fluoxetine  Sepsis  Cognitive impairment  Neural network

中文摘要:

      
目的 探讨氟西汀对脓毒症小鼠认知功能障碍和神经炎症的影响。
方法 SPF级雄性C57BL/6小鼠69只，3～4月龄，体重20～30 g。采用随机数字表法将小鼠分为三组：生理盐水组（NS组）、脓毒症组（S组）和脓毒症+氟西汀组（SF组），每组23只。在小鼠右侧海马组织CA1区植入8-通道线性硅探针记录局部场电位（LFP），研究γ震荡强度变化，并根据“两次打击”学说制备脓毒症小鼠模型。S组和SF组腹腔注射脂多糖（LPS）3 mg/kg，NS组在相同时点腹腔注射等体积生理盐水。注射1 d后，S组和SF组每日暴露在4种随机压力源之下，持续21 d；SF组于注射LPS 1周后每日予氟西汀20 mg/kg，持续至行为学测试结束。压力源暴露结束后，所有小鼠进行行为学测试，测试项目包括旷场实验、Y-迷宫、新奇事物识别实验和糖水偏好实验，分别记录中央区域停留时间和运动距离、Y-迷宫交替率、辨别指数和γ震荡强度、糖水偏好率。糖水偏好试验结束后即刻处死小鼠获得脑组织，采用MSD法检测IL-6、IL-1、IL-10浓度。
结果 与NS组比较，S组运动距离明显延长（P<0.05），Y-迷宫交替率、辨别指数、糖水偏好率明显降低（P<0.05）,γ震荡强度明显减弱（P<0.05），海马组织IL-6浓度明显升高（P<0.05）。与S组比较，SF组运动距离明显缩短（P<0.05），Y-迷宫交替率、辨别指数、糖水偏好率明显升高（P<0.05）,γ震荡强度明显增强（P<0.05），海马组织IL-6浓度明显降低（P<0.05）。三组海马组织IL-1和IL-10 浓度差异无统计学意义。NS组和SF组各项指标差异均无统计学意义。
结论 氟西汀可以改善小鼠行为，降低海马组织促炎因子浓度，改善脓毒症小鼠认知功能。

英文摘要:

      
Objective To investigate the effect of fluoxetine on cognitive dysfunction and neuroinflammation in sepsis mice.
Methods Sixty-nine SPF male C57BL/6 mice, aged 3-4 months and weighing 20-30 g, were divided into 3 groups using random number table: saline group (group NS), sepsis group (group S) and sepsis plus fluoxetine group (group SF), 23 mice in each group. An 8-channel linear in silico probe recording local field potential (LFP) was implanted in the CA1 region of the right hippocampal tissue to investigate changes in γ shock intensity, and a mouse model of sepsis was prepared according to the “two hits” theory. Sepsis mouse model was established according to the theory of “two-hits”. Liopolysaccharide (LPS) 3 mg/kg was injected intraperitoneally in groups S and SF, while group NS was injected with equal volume saline at the same time. One day later, groups S and SF were then randomly exposed to four stressors for 21 consecutive days. One week after LPS injection, group SF was given fluoxetine 20 mg/kg till the end of the behavioral tests. After the completion of the stress exposure, all mice were subjected to behavioral testing, and the test items included absenteeism experiment, Y-maze, novelty identification experiment, and sugar water preference experiment, the central region stay time and motion distance, Y-maze alternating rate, recognition index (RI) and γ shock intensity, sugar water preference rate were recorded. Mice were executed immediately after the sugar water preference test to obtain brain tissue. The concentrations of the IL-6, IL-1, IL-10 were detected by MSD.
Results Compared with the group NS, the travel distance was significantly increased in group S (P < 0.05), the Y-maze alternation rate, RI, sugar-water preference rate and γ shock intensity in group S were significantly decreased (P < 0.05), the level of IL-6 in the hippocampus was significantly increased in group S (P < 0.05). Compared with the group S, the travel distance was significantly decreased in group SF (P < 0.05), the Y-maze alternation rate, RI, sugar-water preference rate and γ shock intensity in group SF were significantly increased (P < 0.05), the level of IL-6 in the hippocampus was significantly decreased in group SF (P < 0.05).There were no significant differences in the level of IL-6 and IL-10 in the hippocampus among the there groups. There were no significant differences between groups NS and SF.
Conclusion Fluoxetine improves mouse behavior, reduces the expression of proinflammatory factors in hippocampal tissue and improves cognitive function in sepsis mice.