慢性间歇性酒精暴露对创伤后应激小鼠恐惧、焦虑和抑郁行为的影响及机制  

Effects and Mechanisms of Chronic Intermittent Alcohol Exposure on Fear,Anxiety and Depression Behavior in Post-Traumatic Stress Mice

作　　者：郝丽艳 张一博 吴杨杏子 徐青青 张议方 袁诗雨 肖一帆 舒细记[1,2,3] 龚晓康[1,2] Hao liyan;Zhang Yibo;Wu Yangxingzi(Hubei Key Laboratory of Cognitive and Affective Disorders,School of Medicine,Jianghan University,Wuhan 430056,China;Wuhan Institutes of Biomedical Sciences,School of Medicine,Jianghan University,Wuhan 430056,China;Department of Pathology and Pathophysiology,School of Medicine,Jianghan University,Wuhan 430056,China)

机构地区：[1]江汉大学医学部认知与情感障碍湖北省重点实验室,武汉430056 [2]江汉大学医学部武汉生物医学研究院,武汉430056 [3]江汉大学医学部基础医学院病理学与病理生理学教研室,武汉430056

出　　处：《华中科技大学学报（医学版）》2024年第5期591-598,共8页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.82001281);江汉大学校级科研项目(No.2022XKZX28)。

摘　　要：目的观察慢性间歇性酒精暴露对创伤后应激障碍(post-traumatic stress disorder,PTSD)小鼠恐惧、焦虑和抑郁行为的影响以及可能的机制。方法将36只8周龄C57雄性小鼠随机分为正常对照(Control)组,创伤后应激(PTSD)组以及创伤后应激慢性间歇性酒精暴露(PTSD+Alcohol)组,利用足底电击法制备小鼠PTSD模型后予以慢性间歇性酒精暴露14 d,检测各组小鼠恐惧、焦虑和抑郁行为;采用Western blot法检测各组小鼠海马组织小胶质细胞标记物离子钙接头蛋白1(IBA1)、神经元突触后致密蛋白95(PSD95)和突触结合蛋白(synaptotagminⅠ,SYT1)表达水平;采用免疫荧光染色法检测各组小鼠海马组织IBA1、突触素(synaptophysin,SYN)表达水平;通过酶联免疫分析(ELISA)检测各组小鼠海马组织肿瘤坏死因子α(TNF-α),白细胞介素6(IL-6)和白细胞介素1β(IL-1β)的释放量。结果与Control组相比,PTSD组小鼠在条件恐惧实验中僵直时间率显著增加,开放臂穿越次数减少,强迫游泳测试中不动时间增加,海马IBA1蛋白表达量以及TNF-α释放增加,SYN、PSD95和SYT1蛋白表达则下降(均P<0.05)。与PTSD组相比,PTSD+Alcohol组小鼠在条件恐惧实验中僵直时间率显著增加,旷场测试运动距离和中央区时间减少,海马IBA1蛋白表达增加,TNF-α和IL-1β释放量增加(均P<0.05)。结论慢性间歇性酒精暴露能够加重创伤后应激小鼠的恐惧、焦虑和抑郁行为,其机制可能与小胶质细胞的激活有关。Objective This study aimed to explore the effects and mechanisms of chronic intermittent exposure to alcohol on fear,anxiety and depression behavior in post-traumatic stress disorder mice.Methods Thirty-six 8-week-old male C57BL/6J mice were randomly divided into a control group(Control),a traumatic stress disorder(PTSD)group and a chronic intermittent alcohol exposure(PTSD+Alcohol)group.The PTSD mice were prepared via the plantar electric shock method and then chronically exposed to alcohol for 14 days.The fear,anxiety and depression behaviors of each group of mice were observed via a behavioral test.Western blotting was used to detect the expression levels of the microglial markers ionized calcium binding adapter molecule 1(IBA1),postsynaptic density protein 95(PSD95),and synaptotagminⅠ(SYT1)in the hippocampal tissue of the mice in each group.Immunofluorescence staining was performed to assess the expression levels of IBA1 and Synaptophysin(SYN)in the hippocampal tissue.An enzyme-linked immunosorbent assay(ELISA)was used to measure the release of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in the hippocampal tissue.Results Compared with those in the control group,the ratio of freezing time in the conditioned fear chamber significantly increased,the number of open arm entries decreased,the immobility time in the forced swim test increased in the PTSD group,and the expression of IBA1 protein and TNF-αrelease increased,with decreased expression of SYN,PSD95 and SYT1(all P<0.05).Compared with the PTSD group,the PTSD+Alcohol group presented significantly increased freezing time in the conditioned fear chamber,decreased locomotor distance and time spent in the center zone in the open field test,increased IBA1 protein expression,and increased release of TNF-αand IL-1β(all P<0.05).Conclusion Chronic intermittent alcohol exposure can aggravate fear,anxiety and depression in post-traumatic stress model mice,and the mechanism may be related to the activation of microglia.

关 键 词：创伤后应激 酒精使用障碍 焦虑 抑郁 小胶质细胞 

分 类 号：R749.5[医药卫生—神经病学与精神病学]