甘麦大枣汤通过调控炎症改善LPS诱导的小鼠急性抑郁样行为

Effect of Ganmai Dazao Decoction on LPS-Induced Acute Depression by Modulating Inflammatory Cytokines in Mice

目的:探究甘麦大枣汤对脂多糖(Lipopolysaccharide,LPS)诱导的小鼠急性抑郁模型的影响。方法:采用LPS建立小鼠急性抑郁模型,观察甘麦大枣汤5、10、20 g/kg组对造模前、后小鼠体重及悬尾、强迫游泳、敞箱实验中行为学变化的影响;应用ELISA法检测小鼠外周血及脑组织炎症细胞因子水平的变化;PCR检测脑内炎性因子相关基因表达水平的变化;利用相关性分析评价小鼠行为学变化与炎症因子水平变化间的关联。结果:与空白组相比,模型组小鼠尾悬实验累计静止不动时间明显延长,敞箱实验运动轨迹总距离显著减少,血清IL-1β、TNF-α、IL-6含量明显升高,IL-10含量明显降低,脑中IL-6含量明显升高,IL-10含量明显降低,脑组织IL-1βmRNA上调,Argl mRNA下调。与模型组相比,甘麦大枣汤20 g/kg能明显减少小鼠悬尾及强迫游泳实验累计静止不动时间,增加运动轨迹总距离;明显降低中枢及外周促炎因子IL-1β、TNF-α、IL-6含量,明显提高IL-10含量;抑制脑组织IL-1βmRNA表达水平。各组小鼠外周IL-1β水平与悬尾累计静止不动时间存在明显正相关,提示炎症水平与抑郁行为相关。结论:甘麦大枣汤可显著改善LPS诱导的急性抑郁样行为,该方对炎症水平的调控作用可能是其改善抑郁症状的作用机制之一。

Objective:To investigate the effect and mechanism of Ganmaidazao Decoction(GMDZD)on Lipopolysaccharide(LPS)-induced acute depression in mice.Methods:Acute depressive mice model was established by LPS.After the administration of GMDZD(2.5,5,10 g/kg),the changes of mice body weights,the behavioral changes in tail suspension test(TST),forced swimming test(FST)and open field test(OFT)were observed before and after modeling.Ezyme-linked immunosorbent assay(ELISA)was used to detect the levels of peripheral and brain inflammatory cytokines.Polymerase Chain Reaction(PCR)was used to detect the relative expression of brain inflammatory-related genes.Correlation analysis was used to evaluate the correlation between the changes of behavior and inflammatory factors.Results:Compared with the control group,the total immobility time in TST was increased,the total distance in OFT were reduced,the contents of serum IL-1β、TNF-αand IL-6 were increased,the content of IL 10 was decreased.The content of IL 6 was increased,while IL 10 was decreased in the brain.In the brain,the mRNA expression of IL-1βwas up regulated,mRNA expression of Argl was down regulated.Compared with the model group,GMDZD had the significant effect on reducing total immobility time in TST and FST,the total distance of motion trajectory in OFT was remarkably increased.Moreover,the levels of pro-inflammatory cytokines IL-1β,TNF-αand IL-6 were inhibited,the level of anti-inflammatory factor IL-10 was increased.The mRNA expression of IL-1βwas reduced in the brain.In addition,correlation analysis showed the significant positive correlation between the level of peripheral IL-1βand the immobility time of TST.Conclusion:GMDZD takes advantages in relieving acute depressive-like behavior,and modulating inflammatory cytokines might be the part of its effective mechanism in treating depressive disorders.