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中国临床药理学与治疗学 ›› 2021, Vol. 26 ›› Issue (5): 539-545.doi: 10.12092/j.issn.1009-2501.2021.05.010

• 基础研究 • 上一篇    下一篇

长春西汀通过Wnt/GSK3β/β-catenin信号通路改善七氟醚麻醉诱导幼鼠远期学习记忆功能

吴畏,陈政,杜真,屈双权   

  1. 湖南省儿童医院麻醉科,长沙 410007,湖南
  • 收稿日期:2020-11-23 修回日期:2021-03-04 出版日期:2021-05-26 发布日期:2021-06-02
  • 通讯作者: 屈双权,男,硕士,主任医师,研究方向:小儿麻醉。 Tel: 13873159261 E-mail: shuangquanqu@126.com
  • 作者简介:吴畏,男,硕士,主治医师,研究方向:手术麻醉基础与临床研究。 Tel: 18673194787 E-mail: yddv0101@163.com
  • 基金资助:
    湖南省卫生健康委课题(20200659)

Vinpocetine improves the long-term cognitive function of infant rats induced by sevoflurane via Wnt/GSK3β/β-catenin signaling pathway

WU Wei, CHEN Zheng, DU Zhen, QU Shuangquan   

  1. Department of Anesthesiology, Hunan Children's Hospital, Changsha 410007, Hunan, China
  • Received:2020-11-23 Revised:2021-03-04 Online:2021-05-26 Published:2021-06-02

摘要: 目的:探讨长春西汀对七氟醚麻醉对幼鼠远期学习与记忆功能的影响及机制。方法:60只SD幼鼠,随机分为对照组、麻醉组、长春西汀低剂量组(5 mg/kg)、长春西汀高剂量组(10 mg/kg)和GSK3β抑制剂组(10 mg/kg),每组12只。麻醉前2 h,各组幼鼠腹腔注射对应剂量药物。除对照组,各组持续吸入4%七氟醚4 h。8周后开始水迷宫实验,应用免疫荧光双染检测幼鼠脑中神经元增殖,Western blot检测海马组织中各蛋白表达。结果:训练初期各组幼鼠潜伏期没有统计学差异,第三天训练中,与对照组相比,麻醉组幼鼠到达平台潜伏期显著增加(P<0.05);第四天训练中,与麻醉组相比,长春西汀与SB216763干预显著减少了幼鼠到达平台潜伏期(P<0.05)。且测试中,与麻醉组相比,10 mg/kg长春西汀与SB216763干预幼鼠首次达到平台潜伏期显著减少(P<0.05),穿越平台次数显著增加(P<0.05)。与此同时,七氟醚麻醉介导了幼鼠BrdU/NeuN阳性细胞数显著减少(P<0.05)。此外,七氟醚介导海马中Wnt3a表达降低、p-GSK3β表达增加、β-catenin表达降低(P<0.05)。而长春西汀与SB216763干预显著逆转了这些细胞与蛋白表达。 结论:长春西汀通过Wnt/GSK3β/β-catenin信号通路改善七氟醚麻醉诱导幼鼠远期学习记忆功能。

关键词: 七氟醚, 幼鼠, 神经发生, GSK3β

Abstract: AIM: To explore the effect and mechanism of Vinfluoxine on long-term learning and memory function in infant mice.  METHODS: Sixty SD infant rats were randomly divided into Control group, Anesthesia group, Vinpocetine group (5 mg/kg), Vinpocetine group (10 mg/kg), GSK3β inhibition group (10 mg/kg) , with 12 infant rats in each group. Two hours before anesthesia, the infant rats in each group were injected with the corresponding drugs. Except for the control group, each group continued to inhale 4% sevoflurane for 4 hours. After 8 weeks, the Morris Water Maze experiments were started. Immunofluorescence double stains were used to detect neuronal proliferation in the brain. Western Blot was used to detect the protein expression in the hippocampus. RESULTS: There was no significant difference in the incubation period of the rats in the early training groups. On the third day of training, compared with the control group, the rats in the anesthesia group reached a significantly increased platform incubation period (P<0.05); In contrast, the intervention of vinpocetine and SB216763 significantly reduced the latency of rats to reach the platform (P<0.05). And in the test, compared with Anesthesia group, the 10 mg/kg vinpocetine and SB216763 intervention rats achieved a significant reduction in the latency of the first time to the platform (P<0.05), and the number of platforms crossing increased significantly (P<0.05). At the same time, sevoflurane anesthesia mediated a significant decrease in the number of BrdU/NeuN positive cells in rats (P<0.05). In addition, sevoflurane mediated a decrease in Wnt3a expression, an increase in p-GSK3β expression, and a decrease in β-catenin expression in the hippocampus (P<0.05). The intervention of vinpocetine and SB216763 significantly reversed the expression of these cells and proteins. CONCLUSION: Vinpocetine improves the long-term learning and memory function of sevoflurane anesthesia-induced infant rats through Wnt/GSK3β/β-catenin signaling pathway.

Key words: sevoflurane, infant rats, neurogenesis, GSK3β

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