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  • 杨潇潇,靳溪源,王清秀,等.全身麻醉下盲肠切除术后小鼠空间学习记忆能力下降的中枢炎症机制[J].同济大学学报(医学版),2020,41(1):41-46.    [点击复制]
  • YANG Xiao-xiao,JIN Xi-yuan,WANG Qing-xiu,et al.Effects of CNS inflammation on spatial learning and memory after cecal resection under general anesthesia in mice[J].同济大学学报(医学版),2020,41(1):41-46.   [点击复制]
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全身麻醉下盲肠切除术后小鼠空间学习记忆能力下降的中枢炎症机制
杨潇潇,靳溪源,王清秀,原源,姚寒,周辰,孙爱莲,蔡红苗
0
(同济大学附属东方医院麻醉科,上海 200120;苏州大学附属第二医院麻醉科,江苏 苏州 215004)
摘要:
目的 对脑内小胶质细胞及TAK1基因的表达上调对空间记忆的影响进行初步探索,为围手术期神经认知障碍(perioperative neurocognitive disorders, PND)中空间学习记忆能力的减退提供神经炎症机制证据。方法 采用8~9月龄C57BL/6J小鼠,异氟醚吸入下行剖腹盲肠切除术建立PND模型与普通型C57BL/6J小鼠作对比。分别在不同时间点利用水迷宫实验检测小鼠的空间记忆。并通过免疫组化技术检测术后小鼠不同脑区小胶质细胞改变及TAK1蛋白表达变化。Western印迹法检测术后小鼠脑内TAK1的表达水平。结果 术后3d前额叶皮层,海马CA2/3、DG区,纹状体区域小胶质细胞胞体增大,数量增多(P<0.05)。术后7d各脑区小胶质细胞数量逐渐下降(P<0.05),至术后15d恢复至术前水平。Western印迹法实验提示术后3d TAK1蛋白在前额叶皮层和海马的表达均增高。术后2d小鼠出现空间学习能力受损,7d出现空间记忆能力受损(P<0.05)。结论 吸入麻醉下盲肠切除术后早期,包括海马区域在内的多个与学习记忆功能相关的脑区,均有明显的小胶质细胞活化和TAK1蛋白表达上调,提示中枢炎症的发生。同时,术后早期,小鼠出现空间学习记忆能力受损,提示腹部手术后PND的发生发展或与记忆相关脑区中枢炎症的发生相关。
关键词:  空间记忆  围手术期神经认知障碍  麻醉  转化生长因子β活化激酶1  盲肠切除
DOI:10.16118/j.1008-0392.2020.01.007
投稿时间:2019-05-28
基金项目:上海市浦东新区卫生系统重要薄弱学科建设资助课题(PWZbr2017-18);上海市重症医学重中之重临床重点学科项目(2017ZZ02017)
Effects of CNS inflammation on spatial learning and memory after cecal resection under general anesthesia in mice
YANG Xiao-xiao,JIN Xi-yuan,WANG Qing-xiu,YUAN Yuan,YAO Han,ZHOU Chen,SUN Ai-lian,CAI Hong-miao
(Dept. of Anesthesiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China;Dept. of Anesthesiology, The Second Affiliated Hospital, Soochow University, Suzhou 215004, Jiangsu Province, China)
Abstract:
Objective To investigate the effects of CNS inflammation on spatial learning and memory after cecal resection under general anesthesia in mice. Methods Perioperative neurocognitive disorder(PND) model was established by caecotomy with isoflurane inhalation in C57BL/6J mice aged 8 to 9 months. The spatial memory of mice was determined by water maze test at different time points. The changes of microglia activation and TAK1 protein expression in different brain regions of mice after operation were detected by immunohistochemical technique. Western blot was used to detect the expression of TAK1 in the brain of mice. Results The spatial learning ability of mice was impaired 2d after operation, and the spatial memory ability was impaired 7d after operation. The amount of activated microglia was significantly increased in hippocampus and striatum 3d after operation. The size of microglial cells in the prefrontal cortex, hippocampal CA2/3, DG region and striatum became larger 3d after operation. The number of microglial cells decreased gradually 7d after operation and finally back to the pre-operation level 15d after surgery. Western blotting showed that the expression of TAK1 protein in prefrontal cortex and hippocampus was increased 3d after operation under inhalation anesthesia. Conclusion In the early postoperative period, mice show impaired spatial learning and memory ability, which is associated with the up-regulation of microglia activation and TAK1 protein expression in several brain regions related to learning and memory, suggesting that the occurrence and development of PND after abdominal surgery under general anesthesia may be related to the occurrence of central inflammation in memory-related brain regions.
Key words:  spatial memory  perioperative neurocognitive disorders  anesthesia  TGF-β-activated kinase 1  cecectomy

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