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TSPO介导YL-IPA08抗创伤后应激障碍作用的药理学研究

尚超 郭颖 丁振春 房鑫鑫 陈小飞 孙立君 朱冉 张黎明 李云峰

军事医学2017,Vol.41Issue(11):898-901,937,5.
军事医学2017,Vol.41Issue(11):898-901,937,5.DOI:10.7644/j.issn.1674-9960.2017.11.007

TSPO介导YL-IPA08抗创伤后应激障碍作用的药理学研究

Translocator protein mediated anti-PTSD effects of YL-IPA08

尚超 1郭颖 2丁振春 1房鑫鑫 1陈小飞 1孙立君 1朱冉 3张黎明 1李云峰1

作者信息

  • 1. 军事科学院军事医学研究院毒物药物研究所,抗毒药物与毒理学国家重点实验室,北京 100850
  • 2. 解放军总医院,北京100853
  • 3. 广西医科大学药学院,南宁530021
  • 折叠

摘要

Abstract

Objective To explore the role of 18 ku translocator protein (TSPO) in the anti-post-traumatic-stress-disorder(PTSD) effects of YL-IPA08 and the value of TSPO as a potential pharmacological target using gene knock out mice.Methods The PCR method was used to genotype TSPO wild type (WT) mice and knock out (KO) mice.Foot shock was used to establish a well-accepted mouse model of PTSD,the open field test (OFT) was used to evaluate the locomotor activity in mice,and freezing measurement was used to evaluate the PTSD-like fear behavior in mice.Results Compared with TSPO WT mice,KO mice had no expressible TSPO gene,but showed similar locomotor activity to WT mice after PTSD modeling.On day 1,day 5 and day 16 after PTSD modeling (day-1-day 0),both WT and KO mice showed significant PTSD-like behavior with enhanced freezing time.However,8 d treatment (day 0-day 7) of YL-IPA08 (0.3 mg/kg,once daily) or positive drug sertraline (15 mg/kg,once daily) after PTSD modeling significantly reduced freezing time selectively in WT mice,but not in KO mice.Conclusion It has been found for the first time that TSPO WT and KO mice can show the same sensitivity to PTSD modeling (namely the same PTSD-like behavior performance).Interestingly,TSPO can mediate the anti-PTSD effects of YL-IPA08.Therefore,the present study provides direct evidence for the value of TSPO as an potential pharmacological target for PTSD.

关键词

18 ku转位蛋白/YL-IPA08/基因敲除/创伤后应激障碍/药理学靶标

Key words

18 ku translocator protein/YL-IPA08/gene knock out/posttraumatic stress disorder/pharmacological target

分类

医药卫生

引用本文复制引用

尚超,郭颖,丁振春,房鑫鑫,陈小飞,孙立君,朱冉,张黎明,李云峰..TSPO介导YL-IPA08抗创伤后应激障碍作用的药理学研究[J].军事医学,2017,41(11):898-901,937,5.

基金项目

全军医学科研“十二五”重大项目 (AWS16J024) (AWS16J024)

国家自然科学基金资助项目(81773708,81173036) (81773708,81173036)

军事医学

OA北大核心CSCDCSTPCD

1674-9960

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