首页|失眠颗粒对疫情后PTSD患者卒中预防作用的网络药理学及动物实验研究

失眠颗粒对疫情后PTSD患者卒中预防作用的网络药理学及动物实验研究

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  • 国家科技期刊平台
  • NETL
  • NSTL
  • 万方数据
目的:采用网络药理学方法和动物实验验证探讨陕西省中医医院院内制剂失眠颗粒治疗疫情后创伤后应激障碍(post-traumatic stress disorder,PTSD)远期预防卒中(stroke)的作用机制.方法:使用TCMIP和BATMAN-TCMTCMSP等数据库筛选失眠颗粒成分中各味中药的有效成分及靶点,基于GEO数据库采用基因表达图谱分析技术通过基因共表达网络分析(WGCNA)获得PTSD和卒中的差异基因.利用R语言软件进行数据挖掘和统计分析,以筛选出PTSD发生卒中的风险基因.将失眠颗粒的靶点与PTSD 发生卒中的风险基因取交集,通过STRING数据库构建靶点互作网络,在Cytoscape软件进行拓扑分析筛选核心靶点,对交集靶点进行GO功能分析和KEGG富集分析,构建"失眠颗粒中药-成分-靶点"网络图,选取核心靶点进行动物实验验证.结果:失眠颗粒筛选出642个化合物成分,对应2 082个靶点,筛选出PTSD发生卒中的风险基因2 379个,通过VENN分析获得失眠颗粒成分和疾病共同靶点165个.PPI分析后最终获得68个关键靶点,即为失眠颗粒治疗PTSD并对卒中远期预防的核心靶点.在CytoNCA进行拓扑分析,排名前 10 的核心靶点分别是MAPK3、MAPK1、NCOA2、MAPK14、NR3C1、RARA、PRKACA、SMARCD3、FOS、FOXO1.KEGG富集分析后得到104条相关通路,GO功能分析得到10条BP通路、10条MF通路和3条CC通路.在动物实验中,与模型组比较,失眠颗粒可明显改善PTSD的焦虑样行为,同时降低p38 MAPK蛋白的表达水平.结论:失眠颗粒通过抑制p38 MAPK介导的MAPK通路来抑制创伤后应激障碍的抑郁焦虑样行为和记忆能力.PTSD患者卒中的发生率高,失眠颗粒通过治疗PTSD并对卒中的远期预防有迹可循.
Network pharmacology and animal experiment study on the prevention effect of insomnia granule on stroke in post-epidemic PTSD patients
Objective:The mechanism of treating post-traumatic stress disorder(PTSD)with insomnia granules in Shaanxi Provincial Hospital of Traditional Chinese Medicine in the long term prevention of stroke was investigated by network pharmacolo-gy and animal experiments.Method:TCMIP and BATMAN-TCMTCMSP databases were used to screen the effective compo-nents and targets of various Chinese herbs in the composition of insomnia particles.The differential genes of PTSD and stroke were obtained by gene coexpression network analysis(WGCNA)based on GEO database and gene expression mapping analysis technology.Data mining and statistical analysis were performed using R language software to screen for risk genes for stroke in PTSD.The target of insomnia particles was intersected with the risk gene of stroke in PTSD.The target interaction network was constructed by using STRING data library.Topological analysis was carried out on Cytoscape software to screen core targets,and GO function analysis and KEGG concentration analysis were carried out on the intersection targets.The core target was selected for animal experiments.Result:The insomnia granules were screened for 642 compound components corresponding to 2 082 tar-gets,and 2 379 risk genes for stroke in PTSD were screened.Totally 165 common targets of insomnia granules components and diseases were obtained by VENN analysis.The PPI analysis sorted out 68 key targets,which are the core targets of insomnia gran-ules for the treatment of PTSD and for the long-term prevention of stroke.Topology analysis was performed at CytoNCA and the top 10 core targets were MAPK3,MAPK1,NCOA2,MAPK14,NR3C1,RARA,PRKACA,SMARCD3,FOS,andFOXO1.KEGG enrichment analysis yielded 104 related pathways,and GO functional analysis yielded 10 BP pathways,10 MF pathways,and 3 CC pathways.In animal experiments,compared with the model group,insomnia granules significantly im-proved anxiety-like behavior in PTSD,and simultaneously reduced the expression level of p38 MAPK protein.Conclusion:In-somnia granules inhibit depressive-anxiety-like behaviors and memory capacity in post-traumatic stress disorder by inhibiting the p38 MAPK-mediated MAPK pathway.The incidence of stroke among patients with PTSD is high,and the effectiveness of insom-nia pellets in treating PTSD and for long-term prevention of stroke is documented.

Insomnia granulesPost-traumatic stress disorderStrokeNetwork pharmacologyGene co-expression net-work analysisMechanism study

张旭、李兰、柏若雪、张莎、程楠、刘婧涵、阚晓茹、陈钧

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陕西中医药大学,陕西 咸阳 712046

陕西省中医医院,陕西 西安 710003

陕西中医药大学基础医学院,陕西 咸阳 712046

失眠颗粒 创伤后应激障碍 卒中 网络药理学 基因共表达网络分析 机制研究

陕西省自然科学基金陕西省中医药管理局课题陕西中医药大学脑病重点实验室开放项目

2023-JC-YB-6562021-ZZ-JC018KF2218

2024

10.13210/j.cnki.jhmu.20240407.001

海南医学院学报
海南医学院

海南医学院学报

CSTPCD北大核心
影响因子：1.068
ISSN：1007-1237
年,卷(期)：2024.30(13)
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