基础医学与临床 ›› 2016, Vol. 36 ›› Issue (5): 604-609.

• 研究论文 • 上一篇    下一篇

RAGE阻断剂FPS-ZM1减轻异氟醚麻醉诱发老龄大鼠认知功能障碍

史成梅1,易端1,李正迁1,郭向阳2   

  1. 1. 北京大学第三医院
    2. 北京大学第三医院麻醉科
  • 收稿日期:2015-09-14 修回日期:2016-03-03 出版日期:2016-05-05 发布日期:2016-04-26
  • 通讯作者: 史成梅 E-mail:chengmei_shi@sina.com
  • 基金资助:
    血脑屏障RAGE及LRP1在异氟醚所致β淀粉样蛋白增高中的作用及机制研究

RAGE inhibitor FPS-ZM1 reduced isoflurane anesthesia induced cognitive dysfunction in aged rats

  • Received:2015-09-14 Revised:2016-03-03 Online:2016-05-05 Published:2016-04-26
  • Contact: Cheng meiSHI E-mail:chengmei_shi@sina.com

摘要: 目的 探讨RAGE阻断剂FPS-ZM1对异氟醚麻醉诱发老龄大鼠认知功能障碍的影响。方法 将老龄大鼠60只,随机分为4组(n=15):NS+O2组、NS+ISO组、FPS-ZM1+ISO组及FPS-ZM1+O2组。NS+O2组及NS+ISO组,侧脑室注射无菌生理盐水10 μL,FPS-ZM1+ISO及FPS-ZM1+O2组,侧脑室注射FPS-ZM1 10 μL(5 g/L)。侧脑室注射后24 h,NS+O2及FPS-ZM1+O2组吸入含有30%氧气的空氧混合气体4 h,FPS-ZM1+ISO及FPS-ZM1+ISO组吸入2%异氟醚+100%氧气4 h。用Morris水迷宫评测大鼠学习和记忆功能, 用免疫组织化学技术观察海马CA1区RAGE及Aβ的表达。结果 与NS+O2组相比,NS+ISO组第1-4 d逃避潜伏期延长、探索时间缩短、海马CA1区RAGE表达上调、Aβ表达上调。与NS+ISO组相比,FPS-ZM1+ISO组第1-4 d逃避潜伏期缩短,探索时间延长,RAGE表达下调、Aβ表达下调。结论 RAGE阻断剂FPS-ZM1可改善异氟醚麻醉诱发老年大鼠认知功能障碍,其机制可能与其抑制海马CA1区Aβ沉积有关。

关键词: FPS-ZM1, RAGE 阻断剂, 异氟醚, 认知功能障碍, 老龄

Abstract: Objective To investigate the effect of FPS-ZM1 on isoflurane anesthesia induced cognitive dysfunction in aged rats. Methods Sixty aged rats were randomly divided into four groups(n=15)as follow: NS+O2、NS+ISO、FPS-ZM1+ISO、FPS-ZM1+O2.The NS+O2 and NS+ISO groups received intracerebroventricular injection of normalsaline 10 μL. The FPS-ZM1+O2 and FPS-ZM1+ISO groups received intracerebroventricular injection of FPS-ZM1 10 μL(5 g/L). 24 hours after intracerebroventricular injection, The NS+O2 and FPS-ZM1+O2 groups inhaled a gas mixture of oxygen and air for 4 h, and the NS+ISO and FPS-ZM1+ISO groups inhaled 2% isoflurane for 4 h. The tests of learning and memory were performed in Morris water maze, RAGE and amyloid β protein(Aβ) expression in hippocampus CA1 area was determined by immunohistochemistry. Results Compared with NS+ISO group, the escaping latency significantly shortened from 1 to 4 day, and the probe time was significantly increased, the time of staying at the original platform quadrant was significantly longer inthe FPS-ZM1+ISO group. In addition, the level of RAGE and Aβ expression of groups FPS-ZM1+ISO in hippocampus CA1 area was significantly reduced. Conclusion FPS-ZM1 may improve the process of spatial learning and memory by inhibiting Aβ expression in hippocampus CA1 area of aged rats.

Key words: FPS-ZM1, RAGE inhibitor, Isoflurane, Cognition disorders, Aged