中国药理学与毒理学杂志2025，Vol.39Issue(11)：813-820,8.DOI:10.3867/j.issn.1000-3002.2025.08628
四逆散对创伤后应激障碍小鼠恐惧和焦虑行为的改善作用及机制
Ameliorative effect and mechanisms of Sini powder against fear and anxiety behaviors in post-traumatic stress disorder mice
摘要
Abstract
OBJECTIVE To investigate the effects of Sini powder(a traditional Chinese medicine formula)on the behavior of post-traumatic stress disorder(PTSD)model mice and explore the potential mechanism of Sini powder against PTSD.METHODS Male C57BL/6 mice were randomly assigned to the normal control group,model group,model+paroxetine 2.43 mg·kg-1 group,and the model+Sini powder(2.184 and 10.92 g·kg-1)groups.Except the normal control group,mice in these groups were subjected to the foot shock(inescapable electric foot shocks administered for 2 consecutive days,at an intensity of 1 mA,lasting 10 s,with a 10 s interval,and 15 shocks per day)to establish a PTSD model.Twenty-four hours prior to modeling,mice in the drug treatment groups were intragastrically adminis-tered corresponding doses of their respective drugs,while the normal control group and model group received an equal volume of saline via intragastric administration,once daily for 30 consecutive days.At different time points after modeling,the effects of the drugs on PTSD-like behaviors were analyzed using the contextual fear conditioning test(on days 7,14 and 48 post-modeling),open field test(on day 40 post-modeling),elevated plus maze test(on days 9 and 39 post-modeling),and sucrose preference test(on day 37 post-modeling).Upon completion of behavioral tests(day 48 post-modeling),brain tissues were collected from mice in the normal control,model,and model+Sinisan(10.92 g·kg-1)groups.Immu-nofluorescence staining was used to observe the number of microglia in the murine hippocampal region.Real-time quantitative PCR(RT-qPCR)was adopted to detect the mRNA expression levels of interleukin-4(IL-4),IL-6,IL-1β,tumor necrosis factor-α(TNF-α),arginase-1(Arg1)and macrophage mannose receptor(CD206)in order to investigate the mechanism of action of the drug.RESULTS Compared with the normal control group,the model group showed a significant increase in the percentage of freezing time,and a significant decrease in the percentage of entries and time spent in the central area of the open field,as well as the percentage of entries and time spent in the open arms of the elevated plus maze,suggesting the success of modeling.Compared with the model group,both the model+paroxetine group and the model+Sini powder group showed a significant decrease in the percentage of freezing time,and a significant increase in the percentage of entries and time spent in the central area of the open field,and in the percentage of entries and time spent in the open arms of the elevated plus maze.Compared with the normal control group,the model group showed a significant increase in the number of microglia in the hippocampal region,and a significant upregulation of IL-6 mRNA expression.Compared with the model group,the model+Sini powder 10.92 g·kg-1 group exhibited a signifi-cantly smaller number of microglia in the hippocampal region,and the expression levels of the inflamma-tory factors IL-6 and TNF-α were significantly decreased.CONCLUSION Sini powder may improve fear and anxiety-like behaviors in PTSD model mice by regulating microglial activation and neuroinflammation.关键词
四逆散/创伤后应激障碍/小胶质细胞活化/神经炎症/条件恐惧/焦虑/抑郁Key words
Sini powder/post-traumatic stress disorder/microglia activation/neuroinflammation/contextual freezing/anxiety/depression分类
医药卫生引用本文复制引用
王亚静,张雪,袁增强,陈建新,李硕硕..四逆散对创伤后应激障碍小鼠恐惧和焦虑行为的改善作用及机制[J].中国药理学与毒理学杂志,2025,39(11):813-820,8.基金项目
国家自然科学基金(8230142661) （8230142661）
北京市自然科学基金(7252090) National Natural Science Foundation of China(8230142661) （7252090）
and Natural Science Foundation of Beijing Municipality(7252090) （7252090）
