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| 米诺环素对术前焦虑小鼠术后炎症反应和认知功能的影响 |
| Effects of minocycline on postoperative inflammatory response and cognitive function in mice with preoperative anxiety |
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| DOI：10.12089/jca.2025.12.012 |
| 中文关键词: 术前焦虑 炎症反应 认知功能 米诺环素 小鼠 |
| 英文关键词: Preoperative anxiety Inflammatory response Cognitive function Minocycline Mice |
| 基金项目:国家自然科学基金面上项目（82271216） |
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| 摘要点击次数: 859 |
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| 中文摘要: |
目的：探讨米诺环素对术前焦虑小鼠术后炎症反应和认知功能的影响。
方法：选择清洁级健康成年雄性C57BL6/J小鼠60只，8～10周龄，体重25～30 g。采用随机数字法将小鼠分为五组：对照组（C组）、手术组（S组）、焦虑暴露组（A组）、术前焦虑+手术组（AS组）和术前焦虑+手术+米诺环素组（ASM组），每组12只。C组不做任何处理；S组行剖腹探查术；A组行单次延长刺激，6 d后完成后续行为学实验；AS组行单次延长刺激，6 d后行剖腹探查术；ASM组在AS组基础上，于术前2 d至术后3 d连续腹腔注射米诺环素50 mg/kg。于术后第6、7、8天分别依次进行旷场实验、新物体识别实验和Y迷宫实验，记录旷场运动距离、旷场中心区域探索时间，计算新物体探索时间百分比和轮替率。行为学结束后取海马组织，采用ELISA法检测海马组织白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）蛋白含量；免疫荧光法检测海马组织小胶质细胞数量。
结果：与C组比较，A组和AS组旷场中心区域探索时间明显缩短（P＜0.05）。与S组比较，AS组术后新物体探索时间百分比和轮替率明显降低，海马组织IL-1β和IL-6蛋白含量明显升高，小胶质细胞数量明显增多（P＜0.05）。与AS组比较，ASM组术后旷场中心区域探索时间明显延长，新物体探索时间百分比和轮替率明显升高，海马组织IL-1β和IL-6蛋白含量明显降低，小胶质细胞数量明显减少（P＜0.05）。
结论：单次延长刺激可诱导小鼠焦虑样行为，术前焦虑会导致剖腹探查小鼠的术后神经炎症和认知功能下降。给予米诺环素抑制小鼠海马内小胶质细胞的活化，可以缓解神经炎症并改善术前焦虑小鼠术后的认知功能。 |
| 英文摘要: |
Objective: To investigate the effects of preoperative anxiety on the postoperative inflammatory response and cognitive function in mice.
Methods: Sixty clean-grade healthy adult male C57BL6/J mice, aged 8-10 weeks, weighing 25-30 g, were selected. The mice were divided into 5 groups by the random number method: control group (group C), surgery group (group S), anxiety exposure group (group A), preoperative anxiety + surgery group (group AS), and preoperative anxiety + surgery + minocycline group (group ASM), 12 mice in each group. The mice in group C received no treatment. The mice in group S underwent laparotomy. The mice in group A received a single prolonged stimulation, and behavioral experiments were conducted 6 days later to establish a preoperative anxiety model. The mice in group AS underwent laparotomy 6 days after the single prolonged stimulation. The mice in group ASM, on the basis of group AS, were intraperitoneally injected with minocycline 50 mg/kg diluted with PBS continuously from preoperative day 2 until postoperative day 3 to inhibit the activation of microglia. On postoperative days 6, 7, and 8, the open field test, novel object recognition test, and Y-maze test were carried out. The distance of open field movement and the exploration time in the central area of the open field were recorded, and the percentage of exploration time for new objects and the alternation were calculated. After the behavioral experiments, the hippocampal tissues were collected. The contents of IL-1β and IL-6 proteins in the hippocampal tissues were determined by ELISA. The number of microglia in the hippocampus were detected by immunofluorescence.
Results: Compared with group S, the exploration time in the central area of the open field in groups A and AS was significantly reduced (P < 0.05). Compared with group S, the novel object exploration percentage and the alternation in group AS after the operation were significantly decreased, the contents of IL-1β and IL-6 proteins in the hippocampal tissues were significantly increased, and the number of microglia was significantly increased (P < 0.05). Compared with group AS, the exploration time in the central area of the open field after the operation in groups ASM was significantly prolonged, the novel object exploration percentage and the alternation were significantly increased, the contents of IL-1β and IL-6 proteins in the hippocampal tissues were significantly decreased, and the number of microglia was significantly reduced (P < 0.05).
Conclusion: A single prolonged stimulation can induce an anxiety-like behavior in mice. Preoperative anxiety can lead to postoperative neuroinflammation and cognitive function decline in mice undergoing laparotomy. Inhibiting the activation of microglia in the hippocampus of mice by minocycline can alleviate neuroinflammation and improve the postoperative cognitive function of mice with preoperative anxiety. |
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