负性情绪应激通过上调白介素-6水平导致小鼠酒精摄入增多  

Negative emotional stress leads to increased alcohol intake via interleukin-6 in mice

作　　者：李翔[1] 李易易 余杭 高锋 王嘉贝 王舰浩 秦冬冬 李芳[1] 刘松燕 陈洪玉 张茜[1] 王雅梅 王志昊 Li Xiang;Li Yiyi;Yu Hang(Department of Neurology,Center for Neurodegenerative Disease Research,Renmin Hospital of Wuhan University,Wuhan 430060)

机构地区：[1]武汉大学人民医院神经内科、武汉大学人民医院神经退行性疾病研究中心,430060

出　　处：《卒中与神经疾病》2023年第6期539-543,556,共6页Stroke and Nervous Diseases

基　　金：国家自然科学基金青年科学基金项目(82101479);国家重点研究计划项目(2021YFA1302400);湖北省实验动物研究领域项目(2022DFE021);武汉大学人民医院交叉创新人才项目(JCRCZN-2022-002)。

摘　　要：目的 探究负面情绪与小鼠酒精消耗之间的关系以及其分子机制。方法 将8周龄野生型C57BL/6J小鼠进行慢性社交挫败实验,通过社交互动评分分组:易感组(即表现出明显负性情绪)和抵抗组(未表现出明显负性情绪),之后进行糖水偏好实验再次验证负面情绪动物模型是否成功,最后观察各组小鼠酒精消耗量以及检测小鼠不同脑区白介素-6(Interleukin-6,IL-6)水平;将压力易感组的8周龄野生型C57BL/6J小鼠(即具有负面情绪小鼠)分成2组,1组腹腔注射Anti-IL-6抗体,另1组注射Anti-IgG,比较2组酒精消耗量。结果 行为学实验发现,相对于对照组和抵抗组,易感组中小鼠的酒精摄入增多(P<0.01);分子生物学实验发现,与对照组和抵抗组比较,易感组小鼠大脑IL-6水平均明显升高(P<0.05或0.01),且IL-6水平升高与酒精消耗的增多呈正比;易感组小鼠注射Anti-IL-6抗体后其酒精消耗明显减少(P<0.05)。结论 IL-6参与负面情绪导致的小鼠酒精摄入增多,使用抗体降低IL-6水平可减少负性情绪所致的酒精摄入增多。ObjectiveTo explore the relationship between negative emotion and alcohol consumption in mice and its molecular mechanism.Methods 8-week-old wild-type C57BL/6J mice were subjected to chronic social defeat stress(CSDS),and were divided into susceptible group and resilient group by social interaction ratios.Then,sucrose preference test(SPT)was conducted to verify the animal model of negative emotion.Finally,alcohol consumption of mice in each group was quantified and IL-6 levels in different brain regions of mice were detected.Wild-type C57BL/6J mice(Mice with negative emotions)of stress-susceptible group at 8 weeks of age were divided into two groups,one with intraperitoneal injection of Anti-IL-6 antibody and the other with intraperitoneal injection of Anti-IgG.Alcohol consumption was compared between the two groups.Results Behavioral experiment showed that alcohol intake of mice in susceptible group increased(P<0.01)compared with control group and resilient group.Molecular biology experiment confirmed that the level of IL-6 in mice brain of susceptible group was significantly increased(P<0.05,P<0.01)compared with control group and resistance group,and there is a positive correlation between upregulation of IL-6 and increased alcohol consumption.After Anti-IL-6 antibody injection,alcohol consumption in the susceptible group was significantly reduced(P<0.05).Conclusion IL-6 is involved in negative emotion in mice with increased alcohol intake.Blocking IL-6 could decrease alcohol intake induced by negative emotional stress.

关 键 词：负面情绪 酒精摄入 白介素-6 慢性社交挫败 社交互动 糖水偏好 

分 类 号：R749.5[医药卫生—神经病学与精神病学]