大麻二酚及其纳米制剂对小鼠抑郁行为的作用  

The effect of cannabidiol and its nano-preparation on depressive behaviors in mice

作　　者：李远萍 谭慧 孟靖源 杨艳 马滕滕 杨正茂 马加庆 谢建平 郭英 Li Yuanping;Tan Hui;Meng Jingyuan;Yang Yan;Ma Tengteng;Yang Zhengmao;Ma Jiaqing;Xie Jianping;Guo Ying(Dept of Pharmacology,Faculty of Basic Medical Science,Kunming Medical University,Kunming 650500;Purui Biomedical Technology Co.,LTD.,Huzhou 313000;Dept of Technical Service,Library,Yunnan Minzu University,Kunming 650500)

机构地区：[1]昆明医科大学基础医学院药理学系,昆明650500 [2]浦瑞生物医药技术有限公司,湖州313000 [3]云南民族大学图书馆技术服务部,昆明650500

出　　处：《安徽医科大学学报》2025年第3期440-445,454,共7页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金资助项目(编号:82060650);云南省中青年学术和技术带头人后备人才项目(编号:202405 AC350045)。

摘　　要：目的研究大麻二酚(CBD)及其纳米制剂对小鼠抑郁样行为的影响及机制。方法腹腔注射脂多糖(LPS)诱导急性焦虑抑郁小鼠模型。将55只小鼠随机分组:长期实验分为正常(Con)组、模型(LPS)组、大麻二酚(CBD)组、纳米大麻二酚(NCBD)组、舍曲林(SER)组,每组7只;短期实验分为Con组、LPS组、CBD组、NCBD组,每组5只。除Con组和LPS组给予蒸馏水,其余组灌胃给予25、50 mg/kg CBD及其纳米制剂。采用旷场和强迫游泳实验检测小鼠焦虑及抑郁样行为,Luxol Fast Blue髓鞘染色检测前额皮层中髓鞘形态,免疫荧光染色检测前额皮层中沉默信息调节因子2(SIRT2)、离子钙结合衔接分子1(Iba-1)和白细胞介素-1β(IL-1β)蛋白表达。结果长期实验中与Con组比较,LPS组小鼠穿梭次数减少(P<0.05),不动时间百分比增加(P<0.01),髓鞘数量及长度减少(P<0.05);与LPS组相比,CBD组、NCBD组、SER组小鼠抑郁样行为减少(P<0.01),髓鞘数量及长度增加(P<0.05)。短期实验中与Con组比较,LPS组小鼠焦虑抑郁样行为增加(P<0.05),SIRT2表达降低(P<0.01),Iba-1、IL-1β表达增加(P<0.01);与LPS组相比,CBD组、NCBD组小鼠焦虑样行为减少(P<0.05),SIRT2表达增加(P<0.01),Iba-1、IL-1β表达降低(P<0.05)。结论CBD及其纳米制剂可缓解小鼠焦虑、抑郁样行为,作用机制可能与逆转前额皮层中SIRT2蛋白表达、脱髓鞘变化、小胶质细胞活化及炎症因子的水平相关。Objective To investigate the therapeutic effects and underlying mechanisms of cannabidiol(CBD)and its nano-formulations on depression-like behaviors in mice.Methods A murine model of acute anxiety and depression was established by intraperitoneal administration of lipopolysaccharide(LPS).A total of 55 mice were randomly assigned into several groups:for the long-term study,a control group(Con),a model group(LPS),a cannabidiol group(CBD),a nano-cannabidiol group(NCBD),and a sertraline(SER)group,each consisting of 7 mice.In the short-term study,mice were divided into four groups:the Con group,LPS group,CBD group,and NCBD group,with 5 mice in each group.Except for the Con group and LPS group,which were given distilled water,the remaining groups were administered 25 and 50 mg/kg of cannabidiol and its nano-formulation via oral gavage.The open field and forced swimming tests were employed to assess anxiety-and depression-like behaviors in mice.Luxol Fast Blue myelin staining was employed to evaluate myelin sheath morphology in the prefrontal cortex,and immunofluorescence staining was utilized to quantify the protein expression levels of silencing information regulator(SIRT2),ionized calcium binding adaptor molecule-1(Iba-1),and interleukin-1β(IL-1β)in the prefrontal cortex.Results In the long-term experiment,the LPS group exhibited a significant reduction in shuttle times(P<0.05),an increase in immobility time(P<0.01),and a decrease in the number and length of myelin sheaths(P<0.05)compared to the Con group.Compared to the LPS group,the depressive behaviors in the CBD,NCBD,and SER groups were significantly alleviated(P<0.01),and the number and length of myelin sheaths increased(P<0.05).In the short-term experiment,compared to the Con group,the LPS group exhibited significantly increased anxiety-and depression-like behaviors(P<0.05),downregulated SIRT2 expression(P<0.01),and upregulated Iba-1 and IL-1βexpression(P<0.01).The CBD and NCBD groups demonstrated a reduction in anxiety and depression-like behaviors(P<0.05),

关 键 词：抑郁样行为 大麻二酚 沉默信息调节因子2 白细胞介素-1β 髓鞘 纳米大麻二酚 离子钙结合衔接分子1 

分 类 号：R965.1[医药卫生—药理学]