机构地区:[1]黑龙江中医药大学附属第一医院,黑龙江哈尔滨150040 [2]黑龙江中医药大学附属第二医院,黑龙江哈尔滨150001 [3]黑龙江中医药大学,黑龙江哈尔滨150040
出 处:《海南医学院学报》2020年第9期677-685,共9页Journal of Hainan Medical University
基 金:黑龙江省自然科学基金(面上项目)(H2017064)。
摘 要:目的:基于网络药理学方法分析三物黄芩汤的主要化合物并预测其治疗白塞病可能作用靶点和机制。方法:通过TCMSP、TCMID和文献检索三物黄芩汤的主要化合物及其相应的作用靶点;通过GeneCards数据库检索白塞病的疾病靶标;三物黄芩汤和白塞病的交集靶点通过String数据库和Cytoscape软件构建网络可视化;利用DAVID数据库对交集靶点进行GO和KEGG富集分析;通过构建BD小鼠模型,RT-PCR法验证三物黄芩汤对把核心靶基因的调控作用。结果:通过数据库共检索到三物黄芩汤主要活性化合物81个,药物-疾病-靶点50个。GO富集分析共得到531条生物功能信息,KEGG共富集到96条信号通路,其中富集程度排名前5的信号通路有Fluid shear stress and atherosclerosis、AGE-RAGE signaling pathway in diabetic complications、IL-17 signaling pathway、TNF signaling pathway、Malaria、Chagas disease(American trypanosomiasis)。RT-PCR结果显示,与空白组比较,BD小鼠脾脏组织中IL-4、IL-1β、IL-6、INF-γmRNA的表达明显上调,Caspase 3和Caspase 8 mRNA的表达显著下调,差异均具有统计学意义(P<0.01)。与模型组相比,三物黄芩汤组小鼠脾脏组织中IL-4、IL-1β、IL-6、INF-γmRNA的表达明显下调,Caspase 3和Caspase 8 mRNA的表达显著上调,差异均具有统计学意义(P<0.01)。结论:三物黄芩汤能够通过多靶点、多通路治疗BD,同时为深入揭示其作用机制和治疗提供了生物信息学基础。Objective:To analyze the main compounds of Sanwu Huangqin decoction based on the method of network pharmacology and to predict its possible target and mechanism of action in the treatment of Behcet's disease(BD).Methods:TCMSP,TCMID and literatures were used to search the main compounds and their corresponding targets of Sanwu Huangqin Decoction;the disease targets of BD were searched by GeneCards database;the intersection targets of Sanwu Huangqin Decoction and BD were visualized by String database and Cytoscape software;the intersection targets were enriched by GO and KEGG by DAVID database;BD mouse model was established,RT-PCR was used to verify the regulatory effect of Sanwu Huangqin Decoction on the core target genes.Results:A total of 81 main active compounds and 50 drug-disease-target were retrieved from the databases.There were 531 pieces of biological function information and 96 signal pathways were enriched by GO and KEGG.Among them,the top 5 signal pathways were Fluid shear stress and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications,IL-17 signaling pathway,TNF signaling pathway,Malaria,Chagas disease(American trypanosomiasis).RT-PCR results showed that the expression of IL-4,IL-1β,IL-6,INF-γmRNA in the spleen of BD mice was significantly up-regulated,and the expression of Caspase 3 and Caspase 8 mRNA was significantly down regulated when compared with the control group(P<0.01).Compared with the model group,the expression of IL-4,IL-1β,IL-6,INF-γmRNA in the Sanwu Huangqin decoction group was significantly down regulated,and the expression of caspase 3 and caspase 8 mRNA was significantly up regulated(P<0.01).Conclusion:Sanwu Huangqin decoction can treat BD through multi-target and multi-channel therapy,and our study and our research provides bioinformatics for further revealing its mechanism and treatment.
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