增强中枢胆碱能神经系统活性对小鼠术后认知障碍的影响

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Abstract Objective To evaluate the effect and mechanism of enhancing the activity of central cholinergic nervous system on postoperative cognitive dysfunction (POCD) in mice. Methods Forty-five C57BL/6 mice were selected and divided into three groups by random number table method, blank group, operation +NS group, operation +Galan group, with 15 mice in each group. The latter two groups underwent internal fixation of unilateral tibial fracture to establish the model of postoperative cognitive dysfunction. In the operation +NS group, 0.9% NaCl was injected into the abdominal cavity every day. Postoperative intraperitoneal injection of central cholinergic neuroactivity enhancer Galan intervention. No surgical or medical intervention was performed in the blank group. The behavioral changes of learning and memory in three groups were assessed by the situational fear test on the third and seventh day after the operation. The activation degree and number of microglia cells in the hippocampus were detected on the third day after the operation. The expression of pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) and anti-inflammatory cytokines (IL-4 and IL-10) in the hippocampus were detected. Results In the behavioral test 3 days after the operation, compared with the blank group, the freezing time in the operation +NS group and the operation +Galan group was significantly reduced (P ＜ 0.01). Compared with the operation +Galan group, the freezing time of the operation +NS group was reduced (P ＜ 0.05). Seven days after the operation, the freezing time of the operation +NS group was significantly reduced compared with the blank group (P ＜ 0.01), and the freezing time of the operation +NS group was shorter than that of the operation +Galan group (P ＜ 0.05), while the difference between the operation +Galan group and the blank group was not statistically significant (P ＞ 0.05). 3 days after the operation, the number of microglia cells in the hippocampus in the operation +NS group was significantly increased compared with the blank group and the operation +Galan group (P ＜ 0.01), but the difference between the blank group and the operation +Galan group was not statistically significant (P ＞ 0.05). Compared with the blank group, IL-1β, IL-6 and TNF-α of the operation +NS group were significantly increased (P ＜ 0.01), and their IL-1β, IL-6 and TNF-α were significantly higher than those of the operation +Galan group (P ＜ 0.01 or P ＜ 0.05). There was no significant difference in IL-1β, IL-6 and TNF-α between the blank group and the operation +Galan group (P ＞ 0.05). There was no significant difference in IL-4 and IL-10 among the three groups (P ＞ 0.05). Conclusion Enhancing the activity of the central cholinergic nervous system can reduce the inflammatory response in the hippocampus by inhibiting the activation of microglia cells in the hippocampus, thus improving the postoperative cognitive ability of mice. Enhancing central cholinergic activity may be a therapeutic strategy for early POCD.

Key words： Postoperative cognitive dysfunction Cholinergic system Inflammatory factors Microglia

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	WANG Tianhai1 ZHU Hongge2 HOU Yanshen1 DUAN Wenming1 YU Chanjuan1

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WANG Tianhai1 ZHU Hongge2 HOU Yanshen1 DUAN Wenming1 YU Chanjuan1. Effect of enhancing the activity of central cholinergic nervous system on postoperative cognitive dysfunction in mice[J]. 中国医药导报, 2019, 16(18): 17-20,41.

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http://www.yiyaodaobao.com.cn/EN/ OR http://www.yiyaodaobao.com.cn/EN/Y2019/V16/I18/17

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