首页|基于网络药理学探讨《古今录验》续命汤治疗中风的机制

基于网络药理学探讨《古今录验》续命汤治疗中风的机制

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目的:通过网络药理学方法探究《古今录验》续命汤治疗中风的潜在作用机制.方法:通过TCMSP数据库检索《古今录验》续命汤中麻黄、当归、桂枝、人参、杏仁、石膏、川芎、干姜、甘草的活性成分及作用靶点;以"cerebral infarc-tion"为关键词检索OMIM、GeneCards、NCBI数据库,进行有效的人类基因检索;利用Venny 2.1软件制作成分靶点与疾病靶点韦恩图,通过STRING数据库构建PPI网络图,并将其引入Cystoscape 3.8.0软件,使用网络分析(network analyzer)方法完成拓扑解析,采用度值(degree)排序方式选择得分超过平均值的靶点作为主要靶点,并启动MCODE模块进行基因组数据分析及核心靶点挑选.使用Cytoscape 3.8.0软件构建成分-疾病-靶点网络图,并进行拓扑分析,以degree值对成分进行排序.采用GO功能富集分析和KEEG通路富集分析对基因进行简单注释,采用R语言及cluster profiler包创建柱形图和气泡图以获取更精确的数据结果.结果:《古今录验》续命汤活性成分共有256个作用靶点,中风靶点1841个,成分与疾病交集靶点158个;运用PPI网络结构结合MCODE算法共筛选出续命汤治疗中风的10个基因簇和9个关键基因,包括胆碱能受体毒蕈碱 1(CHRM1)、胱天蛋白酶9(CASP9)、信号传导及转录激活蛋白(STAT)、缺氧诱导因子(HIF)、氧化低密度脂蛋白受体 1(OLR1)、UDP葡糖醛酸基转移酶1家族多肽A1(UGT1A1)、纤溶酶原激活因子(t-PA)、干扰素调节因子1(IRF1)、基质金属肽酶 3(MMP3)等.GO功能富集分析共富集到2458条生物过程,174项分子功能,109项细胞组分;KEGG通路富集分析得到177条信号通路,续命汤主要通过活性成分槲皮素、木犀草素、山奈酚等与关键靶点结合,作用于血脂和动脉粥样硬化、糖尿病并发症中的衰老信号通路等,达到对脑卒中的有效治疗作用.结论:《古今录验》续命汤治疗中风表现出多元化、多样化的作用特点,通过网络药理学研究为基础理论研究及实践应用指明道路.
Exploration of the mechanism of Xuming Decoction in the treatment of stroke in Gujin Luyan based on network pharmacology
Objective:To explore the potential mechanism of Xuming Decoction in the treatment of stroke in Guj in Luyan by network pharmacology.Methods:The active ingredients and their targets of Mahuang,Danggui,Guizhi,Renshen,Xingren,Shigao,Chuangxiong,Ganjiang and Gancao in Xuming Decoction in Guj in Luyan were searched through TCMSP database."Cerebral infarction"was used as the key word to search OMIM,GeneCards and NCBI database for effective human gene retrieval.Venny 2.1 software was used to produce Venn diagram of component targets and disease targets.The PPI net-work diagram was constructed through the STRING database and introduced into Cystoscape 3.8.0 software.The network ana-lyzer method was used to complete the topology analysis,and the degree ranking method was used to select the targets whose score exceeded the average as the main targets.The MCODE module was started for genomic data analysis and core target se-lection.Cytoscape 3.8.0 software was used to construct component-disease-target network diagram and perform topological analysis to rank the components by degree.GO functional enrichment analysis and KEEG pathway enrichment analysis were used for simple annotation of genes.R language and cluster profiler package were used to create column diagrams and bubble diagrams to obtain more accurate data results.Results:The active ingredients of Xuming Decoction in Guj in Luyan had 256 targets,1841 targets for stroke,and 158 targets for intersection between ingredients and diseases.PPI network structure com-bined with MCODE algorithm were used to screen out 10 gene clusters and 9 key genes in the treatment of stroke by Xuming Decoction,including the cholinergic receptor muscarine 1(CHRM1),caspase 9(CASP9),signal transducer and activator of transcription proteins(STAT),hypoxia-inducible factor(HIF),oxidized low-density lipoprotein receptor 1(OLR1),UDP glucuronyltransferase 1 family polypeptides A1(UGT1A1),plasminogen activator(t-PA),interferon regulatory factor 1(IRF1),and matrix metallopeptidase 3(MMP3),etc.GO functional enrichment analysis enriched 2458 biological pro-cesses,174 molecular functions and 109 cellular components.KEGG pathway enrichment analysis obtained 177 signaling pathways.Through the combination of active ingredients quercetin,luteolin,kaempferol and other key targets,the Xuming Decoction acted on blood lipids and aging signaling pathways in atherosclerosis and diabetes complications to achieve effective treatment of stroke.Conclusion:The Xuming Decoction in Guj in Luyan has diversified therapeutic characteristics.The re-search of network pharmacology points out the way for the basic theoretical research and practical application.

strokeXuming DecoctionGujin Luyannetwork pharmacologymechanism of action

杨伟、丰云、伍睿昕、吴积海、董昌盛

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河南省泌阳县人民医院,河南 泌阳 463700

上海市闵行区梅陇社区卫生服务中心,上海 201104

上海中医药大学基础医学院,上海 201203

上海中医药大学研究生院,上海 201203

上海中医药大学附属龙华医院肿瘤科,上海 200032

上海市中医药研究院中医肿瘤研究所,上海 200032

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中风 续命汤 《古今录验》 网络药理学 作用机制

上海中医药大学中青年杏林人才培养体系杏林青年学者项目上海市卫生健康委卫生行业临床研究专项上海市科委"科技创新行动计划"生物医药科技支撑专项上海中医药大学紧急应对奥密克戎感染新冠肺炎科研攻关专项(2022)

RC-2017-02-0220204015520S319041002022YJ-49

2024

山西中医药大学学报

山西中医药大学学报

ISSN:
年,卷(期):2024.25(2)
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