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基于网络药理学和动物实验的痴呆健脑方治疗血管性痴呆作用机制研究 |
Based on network pharmacology and animal experiments to explore the mechanism of Chidai Jiannao Formula on the treatment of vascular dementia |
投稿时间:2022-12-29 录用日期:2023-01-11 |
DOI: |
中文关键词: 血管性痴呆 痴呆健脑方 网络药理学 炎症 NF-B信号通路 |
英文关键词: vascular dementia Chidai Jiannao Formula network pharmacology Inflammation NF-B |
基金项目:河南省科技攻关;河南省中医药科学研究专项课题重点项目;河南省中医药科学研究专项课题重大专项;第七批全国名老中医药专家学术经验继承工作项目 |
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中文摘要: |
目的 探寻痴呆健脑方治疗血管性痴呆的有效物质基础和作用机制。方法 网络药理分析:在TCMSP平台、化源网筛选痴呆健脑方活性成分,预测可能作用靶点;将靶点数据录入Uniprot数据库,匹配标准化基因。在OMIM、GeneBank数据库检索血管性痴呆作用靶点,制作“药物-成分-靶点”网络图,记录疾病和药物交集靶点,使用STRING平台分析蛋白间相互关系。利用Metascope数据库对两者交集靶点进行KEGG通路富集和GO生物功能分析。实验验证:Morris水迷宫实验检测大鼠空间学习记忆能力;大鼠海马区检测IL-1β、IL-6、IL-18、TNF-α炎性因子表达,NF-B、p65/p50蛋白水平。结果 以OB≥30且DL≥0.18为条件筛选出痴呆健脑方有效活性成分119个、相关靶点133个,在OMIM、GeneBank数据库检索出血管性痴呆靶点208个,通过Venn图获取疾病与药物交集靶点10个。P富集分析获取GO条目867条,其中生物过程730条、分子功能90条、细胞组分47条;KEGG富集获取信号通路26条。实验验证显示,痴呆健脑方可有效改善血管性痴呆大鼠空间学习记忆能力,降低海马区IL-1β、IL-6、IL-18、TNF-α等炎性因子表达和NF-B、p65/p50蛋白水平,与网络药理学部分预测结果可实现相互印证。结论 痴呆健脑方可通过调控NF-κB信号通路,降低大鼠海马区炎性因子表达,抑制神经炎症反应,改善血管性痴呆临床症状。 |
英文摘要: |
Objective To explore the effective material basis and mechanism of Chidai Jiannao Formula in the treatment of VD.Methods Network pharmacological analysis: The active components of Chidai Jiannao Formula were screened on TCMSP platform and huayuan.com to predict possible targets.The target data were entered into UniProt database to match the standardized genes. Search the target of VD in OMIM and GeneBank databases, make a "drug component target" network diagram, record the intersection target of disease and drug, and analyze the relationship between proteins using STRING platform. Using Metascope database, KEGG analysis and GO biological function analysis were performed on two intersection targets.Experimental verification: Morris test was used to detect the spatial learning and memory ability of rats. IL-1β、IL-6、IL-18、TNF-α、NF-B and p65/p50 was detected. Results with OB ≥ 30 and DL ≥ 0.18, 119 effective active ingredients and 133 related targets of Chidai Jiannao Formula were screened. 208 vascular dementia targets were retrieved from OMIM and GeneBank databases, and 10 intersection targets of disease and drug were obtained from Venn map. P enrichment analysis obtained 867GO items, including 730 biological processes, 90 molecular functions and 47 cell components. 26 signal pathways were obtained by KEGG. Experimental verification: Chidai Jiannao Formula could effectively improve the spatial learning and memory ability of vascular dementia rats and reduce IL-1β、IL-6、IL-18、TNF-α、NF-B、and p65/p50, Which were mutually confirmed with the prediction results of network pharmacology. Conclusion Chidai Jiannao Formula can regulate NF-κB signal pathway, reduce the expression of inflammatory factors in rat hippocampus, inhibit neuroinflammatory response, to improve the clinical symptoms of VD. |
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