基于网络药理学研究地奥司明缓解PTSD小鼠焦虑的分子机制
Mechanism of diosmin in alleviating anxiety of PTSD-like mice based on network pharmacology
张新超 1李红玉 2武明媚3
作者信息
- 1. 西北大学生命科学学院,西安 710069;空军军医大学基础医学院神经生物学教研室,西安 710032
- 2. 陕西中医药大学药学院,咸阳 712046
- 3. 空军军医大学基础医学院神经生物学教研室,西安 710032
- 折叠
摘要
目的:探讨地奥司明(DSM)对小鼠创伤后应激障碍(PTSD)焦虑行为的缓解作用及结合网络药理学探讨DSM潜在的作用靶点及机制.方法:利用连续性的束缚、强迫游泳、麻醉和电击小鼠,建立PTSD样小鼠模型;通过腹膜腔注射基于DSM处理.通过旷场、高架动物行为学检测,确定DSM对PTSD样小鼠焦虑行为的缓解作用.使用Swiss Target Prediction、Drug Bank、TTD、Gene Cards等数据库收集DSM和PTSD的相关靶点,利用Venny2.1筛选出DSM成分与PTSD疾病共有靶点,对共有靶点进行PPI网络构建及拓扑学分析确定核心靶点;对核心靶点GO分类富集和KEGG通路富集分析,构建出DSM抗PTSD"成分-疾病-靶标-通路"网络;通过小鼠脑组织免疫荧光染色实验,验证核心靶点.结果:DSM显著缓解PTSD样小鼠的焦虑行为.在DSM与PTSD的网络药理学中有共同靶点53个、核心靶点15个、649个生物过程和46个差异信号通路;筛选度值相对较高的几个关键靶点CCL5、JNK、TNF-α进行小鼠脑片的免疫荧光染色,结果显示与正常对照组相比,PTSD样小鼠海马区这3个蛋白高表达,而DSM可以显著降低它们的表达.结论:DSM可显著缓解PTSD样小鼠的焦虑行为,其作用机制可能与抑制炎症免疫反应密切相关.
Abstract
Objective:Investigate the potential of diosmin(DSM)in alleviating anxiety behavior associated with post-traumatic stress disorder(PTSD)in mice.Methods:A PTSD-like mouse model was induced with continuous restraint,forced swimming,anesthesia,and electric shock.DSM was administered via intraperitoneal injection.The impact of DSM on anxiety behavior was assessed using open-field and elevated maze tests.Databases such as Swiss Tar-get Prediction,Drug Bank,TTD,and Gene Cards were utilized to gather the pertinent targets associated with DSM and PTSD.The Venny2.1 tool was employed to identify overlapping targets between DSM components and those relevant to PTSD.A protein-protein interaction(PPI)network was constructed and topological analysis was conducted to identify core targets.The core targets were further analyzed through GO classification and KEGG pathway enrichment.The"component-disease-target-pathway"network of DSM anti-PTSD was constructed.Immunofluorescence staining of mouse brain tissue was used to verify the core targets.Results:DSM significantly alleviates anxiety-like behavior in PTSD-like mice.The result of network pharmacology revealed 53 common targets,15 key targets,649 biological proces-ses,and 46 differential signaling pathways of DSM in the treatment of PTSD.Key targets CCL5,JNK,and TNF-α with relatively high screening values were used for immunofluorescence staining of mouse brain slices.The expression of CCL5,JNK,and TNF-α were highly higher in the PTSD group than the normal group,and DSM could significantly in-hibit their expression in PTSD-Like mice.Conclusion:DSM can significantly alleviate anxiety-like behaviors in PTSD-like mice,and its mechanism of action may be closely related to the inhibition of inflammatory immune response.
关键词
创伤后应激障碍/地奥司明/网络药理学/动物行为学/小鼠Key words
diosmin/post-traumatic stress disorder/network pharmacology/animal ethology/mouse引用本文复制引用
基金项目
科技创新2030-"脑科学与类脑研究"重点课题(2021ZD0203104)
出版年
2024
NETL
NSTL
万方数据