ISRIB对高原低氧暴露下神经元树突棘形态的保护作用  

Protective effect of ISRIB on dendritic spine morphological changes of neurons exposed to high altitude hypoxia

作　　者：孙亚菲 翟茂登 谭志策 张昊炜 张文斌 张建彬 邹远康 SUN Yafei;ZHAI Maodeng;TAN Zhice;ZHANG Haowei;ZHANG Wenbin;ZHANG Jianbin;ZOU Yuankang(Ministry-of-Education Key Laboratory of Hazard Assessment and Control in Special Operational Environment,Department of Occupational and Environmental Health,School of Military Preventive Medicine,Air Force Medical University,Xi'an 710032,China;Cadet Regiment,School of Basic Medical Sciences,Air Force Medical University,Xi'an 710032,China;School of Public Health,China Medical University,Shenyang 110122,China)

机构地区：[1]空军军医大学军事预防医学系军队劳动与环境卫生学教研室,特殊作业环境危害评估与防治教育部重点实验室,陕西西安710032 [2]空军军医大学基础医学院学员队,陕西西安710032 [3]中国医科大学公共卫生学院,辽宁沈阳110122

出　　处：《空军军医大学学报》2022年第6期685-689,共5页Journal of Air Force Medical University

基　　金：军队后勤科研重大课题(AWS14L008,AWS16J022)。

摘　　要：目的探究整合应激反应抑制剂(ISRIB)对高原低氧暴露下神经元树突棘形态的保护作用。方法将6~8周龄雄性C57BL/6小鼠随机分为常氧组、常氧DMSO组、常氧ISRIB组、高原低氧组、高原低氧DMSO组、高原低氧ISRIB组,每组6只。高原低氧3个组置于低氧舱模拟6000 m高原海拔,连续低氧暴露14 d后,进行小鼠空间学习记忆能力检测,之后利用高尔基染色技术观察各组小鼠海马CA1区神经元树突棘形态及数目变化。结果与常氧组相比,高原低氧暴露引起小鼠学习记忆功能损害(P<0.05),小鼠海马CA1区神经元树突棘密度显著降低(P<0.05),基树突棘与顶树突棘长度显著缩短(P<0.05);给予ISRIB治疗后,高原低氧暴露引起小鼠学习记忆功能损害显著改善(P<0.05),小鼠海马CA1区神经元树突棘密度显著升高(P<0.05),基树突棘和顶树突棘的长度基本恢复正常(P<0.05)。结论ISRIB可保护高原低氧暴露诱导的学习记忆能力损伤及海马CA1区神经元树突棘形态的变化。Objective To investigate the protective effect of integrated stress response inhibitor(ISRIB)on dendritic spine morphological changes of neurons exposed to high altitude hypoxia.Methods C57BL/6 male mice aged 6-8 weeks were randomly divided into normoxia group,normoxia DMSO group,normoxia ISRIB group,high altitude hypoxia group,high altitude hypoxia DMSO group and high altitude hypoxia ISRIB group.The three high altitude hypoxia groups were placed in a hypoxic chamber to simulate the plateau at an altitude of 6000 m.After 14 d of continuous hypoxia exposure,the spatial learning and memory ability of mice was tested.Then,the changes of morphology and number of dendritic spines of neurons in the hippocampal CA1 region of mice in each group were observed by Golgi staining assay.Results Compared with normoxia group,high altitude hypoxia exposure induced impaired learning and memory function(P<0.05),the density of dendritic spines of neurons in hippocampal CA1 region of mice significantly decreased(P<0.05),and the length of basal and apical dendritic spines decreased significantly(P<0.05).After treatment with ISRIB,learning and memory impairment in mice induced by high altitude hypoxia exposure significantly improved(P<0.05),the density of dendritic spines of neurons in hippocampal CA1 region of mice significantly increased(P<0.05),and the length of basal and apical dendritic spines was almost normal(P<0.05).Conclusion ISRIB can protect the learning and memory impairment induced by high altitude hypoxia exposure and the morphological changes of dendritic spines of neurons in hippocampal CA1 region.

关 键 词：ISRIB 海马 树突棘 高原低氧 

分 类 号：R338[医药卫生—人体生理学]