慢性束缚应激模型诱致抑郁和痛敏的行为学研究  

Behavioral study on depression and hyperalgesia induced by chronic restraint stress model

作　　者：杨新江 李嘉琳 丁慧 徐蕾 刘万能 王菲 罗层 YANG Xinjiang;LI Jialin;DING Hui;XU Lei;LIU Wanneng;WANG Fei;LUO Ceng(Department of Neurobiology,School of Basic Medical Sciences,Air Force Medical University,Xi'an 710032,China;Department of Rehabilitation and Physical Therapy,Xijing Hospital,Air Force Medical University,Xi'an 710032,China;College of Life Sciences,Northwest University,Xi'an 710069,China;Battalion 16,No.4 Cadet Regiment,School of Basic Medical Sciences,Air Force Medical University,Xi'an 710032,China;Medical Experimental Center,Shaanxi University of Chinese Medicine,Xianyang 712046,China)

机构地区：[1]空军军医大学基础医学院神经生物学教研室,陕西西安710032 [2]空军军医大学西京医院康复理疗科,陕西西安710032 [3]西北大学生命科学学院,陕西西安710069 [4]空军军医大学学员四大队十六队,陕西西安710032 [5]陕西中医药大学医学科研实验中心,陕西咸阳712046

出　　处：《空军军医大学学报》2023年第11期1059-1063,共5页Journal of Air Force Medical University

基　　金：国家自然科学基金(32071002,82201370);陕西省科技创新团队项目(2022TD-49)。

摘　　要：目的构建伴有慢性疼痛症状的抑郁小鼠模型,为探究抑郁疼痛共病的神经生物学机制和建立临床治疗方案奠定基础。方法将雄性成年C57BL/6J小鼠随机分为两组,分别为慢性束缚应激(CRS)组和假手术(Sham)组,在构建CRS模型21、28、35 d后检测小鼠是否产生抑郁样行为,从而明确小鼠出现抑郁表型的时间节点,并对抑郁小鼠进行旷场、高架十字迷宫实验检测其焦虑样行为;为了观察抑郁是否诱致小鼠产生痛觉敏化,采用von Frey纤维丝与Hargreaves热敏测试箱对产生抑郁的小鼠进行疼痛行为检测。通过组织免疫荧光染色技术观察外侧缰核(LHb)神经元c-Fos表达变化。结果与Sham组相比,CRS组小鼠在持续造模35 d后产生明显的抑郁、焦虑样行为(P<0.05,P<0.01),同时产生显著的机械痛敏与热痛敏(P<0.01);组织免疫荧光染色结果显示CRS组小鼠LHb神经元c-Fos表达显著增多(P<0.01)。结论CRS诱致小鼠产生明显的抑郁、焦虑样行为及痛觉敏化,可作为抑郁疼痛共病的动物模型,LHb可能在其中发挥重要作用。Objective To establish a mouse model of depression with chronic pain symptoms,so as to lay a foundation for exploring neurobiological mechanisms and treatment strategies of depression and pain comorbidity.Methods Adult male C57BL/6J mice were randomly divided into two groups:chronic restraint stress(CRS)group and Sham group.The mice were tested for depressive-like behaviors after CRS at 21,28 and 35 d to determine at which time point the depressive phenotypes appear.The open field test and elevated plus maze test were performed to detect anxiety-like behaviors of depressed mice.In order to observe whether depression induced hyperalgesia in mice,von Frey filaments and Hargreaves test were used to detect pain behaviors of depressed mice.Changes in c-Fos expression in lateral habenula(LHb)neurons were observed using immunofluorescence staining.Results Compared with the Sham group,mice in the CRS group exhibited significant depressive-and anxiety-like behaviors(P<0.05,P<0.01)and significant mechanical and thermal hyperalgesia(P<0.01)after 35 d of continuous modeling.The results of immunofluorescence staining showed significant increase in c-Fos expression in LHb neurons of CRS mice(P<0.01).Conclusion CRS induces significant depressive-and anxiety-like behaviors as well as hyperalgesia in mice,making it a potential animal model for depression and pain comorbidity,in which LHb may play an important role.

关 键 词：慢性束缚应激 抑郁 痛觉敏化 外侧缰核 动物模型 

分 类 号：R-332[医药卫生] R749