模拟高原缺氧条件引起小鼠焦虑与抑郁样行为的研究  

Simulated high altitude hypoxia induces anxiety-and depression-like behaviors in mice

作　　者：赵敬会[1] 王炼 肖锐[1] 阮若彤 刘天曜 李欣[1] 蔡云[1] 范晓棠[1] ZHAO Jinghui;WANG Lian;XIAO Rui;RUAN Ruotong;LIU Tianyao;LI Xin;CAI Yun;FAN Xiaotang(Department of Military Cognitive Psychology,Cdlege of Medical Psychology,Army Medical University(Third Military Medical University),Chongqing,400038,China)

机构地区：[1]陆军军医大学(第三军医大学)医学心理系军事认知心理学教研室,重庆400038

出　　处：《第三军医大学学报》2021年第18期1806-1812,共7页Journal of Third Military Medical University

基　　金：极端环境医学教育部重点实验室开放课题(KL2019GY003);陆军军医大学军事医学预研项目(2018XYY08)。

摘　　要：目的探讨模拟高原缺氧条件对小鼠焦虑样行为以及抑郁样行为的影响。方法选用C57成年雄性小鼠,分为3组(n=10):平原对照组,24 h高原缺氧组,7 d高原缺氧组。行为学方法检测小鼠焦虑样行为、小鼠短期记忆以及小鼠抑郁样行为;免疫组化检测小鼠下丘脑室旁核C-Fos、AVP和GR免疫反应阳性细胞数量;酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)法检测血液中促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)、皮质酮浓度。结果高架十字迷宫实验结果表明7 d高原缺氧组小鼠与对照组相比,开臂时间百分比下降,焦虑样行为增加。悬尾实验表明,7 d高原缺氧组小鼠与对照组相比不动时间增多,抑郁样行为增加(P<0.01)。强迫游泳实验结果显示,24 h高原缺氧处理组小鼠不动时间较对照组显著增加,抑郁样行为增加(P<0.05)。免疫组化结果表明:7 d高原缺氧组小鼠下丘脑室旁核C-Fos蛋白被明显激活。7 d高原缺氧处理小鼠下丘脑室旁核AVP神经元数量、GR阳性数量增加(P<0.01);7 d高原缺氧组小鼠与对照组小鼠相比血液ACTH浓度升高(P<0.05)、24 h高原缺氧处理组小鼠皮质酮浓度上升(P<0.05)。结论急进高原会引起小鼠焦虑和抑郁样行为,且下丘脑-垂体-肾上腺轴对该应激反应进行调节。Objective To determine the effects of simulated altitude hypoxia conditions on anxiety-and depression-like behaviors in mice.Methods C57 adult male mice were divided into 3 groups(n=10):plain control group,24 h plateau hypoxia group,and 7 d plateau hypoxia group.Behavioral observations were used to detect anxiety-like behaviors,short-term memory,and depression-like behaviors in the mice.Immunohistochemical assay was applied to measure the number of C-Fos,AVP and GR immunoreactive cells in the paraventricular nucleus of the hypothalamus.Enzyme linked immunosorbent assay(ELISA)was adopted to detect the concentrations of adrenocorticotropic hormone(ACTH)and corticosterone in the blood.Results The results of the elevated plus maze test showed that the mice in the 7 d plateau hypoxia group had a lower percentage of open arm time and increased anxiety-like behavior than those of the control group.Tail suspension test indicated that the mice of the 7 d plateau hypoxia group had more immobile time and increased depression-like behavior than those of the control group(P<0.01).In the forced swimming test,the 24 h hypoxia group had significantly longer immobility time and increased depression-like behavior than the control group(P<0.05).Immunohistochemical assay showed that the C-Fos protein in the paraventricular nucleus of the hypothalamus was significantly activated in the 7-d plateau hypoxia group.The numbers of AVP and GR positive neurons were increased in the paraventricular nucleus of the hypothalamus in the 7 d plateau hypoxia group(P<0.01).Compared with the control group,the ACTH concentration of mice was elevated in the 7 d plateau hypoxia group(P<0.05),so was the corticosterone concentration in the mice in the 24 h plateau hypoxia group(P<0.05).Conclusion Rapidly entering the high altitude can cause anxiety-and depression-like behaviors in mice,and the stress responses are regulated by the hypothalamic-pituitary-adrenal axis.

关 键 词：高原缺氧 焦虑 抑郁 下丘脑 小鼠 

分 类 号：R339.54[医药卫生—人体生理学] R363.274[医药卫生—基础医学]