大麻二酚通过抑制小胶质细胞激活缓解小鼠焦虑和抑郁样症状  

Cannabinoid alleviates anxiety-and depression-like behaviors in mice via inhibiting microglia activation

作　　者：王嘉宁 秦巧臻 洪顺明 杜张珍 罗常溢 王妍 江小霞 毛更生[1] Wang Jianing;Qin Qiaozhen;Hong Shunming;Du Zhangzhen;Luo Changyi;Wang Yan;Jiang Xiaoxia;Mao Gengsheng(Clinical College of Armed Police General Hospital(The Third Medical Center of PLA General Hospital),Beijing 100853,China;Institute of Military Cognition and Brain Science,Academy of Military Medicine,Academy of Military Sciences,Beijing 100850,China)

机构地区：[1]安徽医科大学武警总医院临床学院(解放军总医院第三医学中心),北京100853 [2]军事科学院军事医学研究院军事认知与脑科学研究所,北京100850

出　　处：《中华微生物学和免疫学杂志》2022年第7期510-519,共10页Chinese Journal of Microbiology and Immunology

基　　金：北京市自然科学基金面上项目(7202149);国家自然科学基金面上项目(31971285)。

摘　　要：目的探讨大麻二酚(cannabinoid,CBD)对脂多糖(lipopolysaccharide,LPS)诱导的小鼠焦虑和抑郁样行为的作用和机制。方法腹腔注射LPS建立神经炎症诱导的C57BL/6J小鼠焦虑和抑郁模型,对造模成功小鼠腹腔注射CBD,行为学试验评价小鼠的焦虑和抑郁样行为,qRT-PCR方法检测小鼠皮层、海马和前额叶皮层中的肿瘤坏死因子α(tumor necrosis factorα,TNF-α)、白细胞介素1β(interleukin-1β,IL-1β)以及CD86的表达水平。体外LPS刺激CBD预处理的小胶质细胞系BV-2,定量PCR方法检测BV-2细胞中TNF-α、IL-1β以及CD86的表达水平。蛋白质印记法检测小鼠不同脑区和BV-2细胞核因子κB(nuclear factor kappa-B,NF-κB)的表达水平。结果CBD显著提高了LPS组小鼠在开放旷场试验(open filed test,OFT)中央区的停留时间和中央区运动路程,显著降低了悬尾试验(tail suspension test,TST)与强迫游泳试验(force swimming test,FST)中的不动时间。同时,CBD还能降低LPS组小鼠大脑的炎症水平和小胶质细胞的活化程度。体外试验提示CBD预处理BV-2细胞后,细胞的活化水平显著降低。体内和体外试验结果均显示CBD能抑制NF-κB的表达水平。结论LPS可诱导BV-2细胞激活及小鼠脑内炎症因子显著升高并出现行为学异常;CBD能抑制小胶质细胞激活,降低LPS诱导的小鼠不同脑区炎症因子表达水平和逆转小鼠焦虑和抑郁样行为。Objective To investigate the effects and mechanism of cannabinoid(CBD)on the anxiety-and depression-like behaviors induced by lipopolysaccharide(LPS)in mice.Methods C57BL/6J mice were intraperitoneally injected with LPS to establish the model of neuroinflammation.CBD was injected intraperitoneally 24 h after modeling.Behavioral tests were performed to evaluate the anxiety-and depression-like behaviors in mice.CBD-pretreated BV-2 microglia cells were stimulated with LPS in vitro.The levels of tumor necrosis factorα(TNF-α),interleukin-1β(IL-1β)and CD86 in mouse cerebral cortex,hippocampus,prefrontal cortex and BV-2 cells were measured by qRT-PCR.The protein level of nuclear factor(NF-κB)in mouse brain and BV-2 cells was determined by Western blot.Results CBD significantly increased the residence time and movement distance of LPS-treated mice in the central area in the open filed test(OFT),and reduced the immobility time in tail suspension test(TST)and force swimming test(FST).In addition,CBD alleviated the neuroinflammation and inhibited the activation of microglia in mouse brain.In vitro,CBD significantly inhibited the activation of BV-2 microglia cells.Both in vivo and in vitro experiments confirmed that CBD could inhibit NF-κB expression.Conclusions LPS could induce the activation of BV-2 microglia cells and the expression of inflammatory factors in mouse brain accompanied with abnormal behaviors.CBD could inhibit the activation of microglia,alleviate the neuroinflammation in different regions of mouse brain and improve behavioral performance.

关 键 词：大麻二酚 小胶质细胞 焦虑 抑郁 脂多糖 

分 类 号：R965[医药卫生—药理学]