真武汤治疗慢性心力衰竭潜在靶点及作用机制的网络药理学研究  

Potential Targets and Mechanism of Zhenwu Decoctionagainst Chronic Heart Failure:Based on Network Pharmacology

作　　者：张冠薇 靳宏光 黄永生[2] 郭家娟[2] ZHANG Guan-wei;JIN Hong-guang;HUANG Yong-sheng;GUO Jia-juan(Changchun University of Chinese Medicine,ChangchunJilin 130021;The Affiliated Hospital to Changchun University ofChinese Medicine,Changchun Jilin 130021)

机构地区：[1]长春中医药大学,吉林长春130021 [2]长春中医药大学附属医院,吉林长春130021

出　　处：《世界中西医结合杂志》2022年第6期1071-1078,共8页World Journal of Integrated Traditional and Western Medicine

基　　金：国家中医药管理局第六批全国老中医药专家学术经验继承项目;吉林省中医药管理局资助项目(2020096);长春中医药大学高层次人才基金项目(2018KJ23)。

摘　　要：目的基于网络药理学方法探讨真武汤治疗慢性心力衰竭的可能作用机制。方法运用TCMSP分析平台、GeneCards、GisGeNET、OMIM数据库,分别筛选真武汤中各组药物的活性成分、靶标及疾病靶标,将药物靶标与疾病靶标取交集,并构建药物-成分-靶点-疾病相互作用网络图及蛋白相互作用网络图,找到关键靶点,并对关键靶点进行GO功能富集分析和KEGG通路富集分析。结果筛选得到真武汤治疗慢性心力衰竭的有效靶标18个,在PPI网络分析中,筛选关键靶点12个,分别为IL-1β、PPARG、ALB、IL-6、HMOX1、MMP2、TGFB1、TP53、STAT1、MMP1、MMP9、VEGFA。其中MMP2、MMP1、MMP9均为基质金属蛋白酶。通过GO功能富集分析可知,真武汤治疗CHF效应的发挥主要在蛋白质细胞外基质的细胞组分上;关于分子生物学功能主要包括金属内肽酶活性、细胞因子活性、酶结合、相同的蛋白质结合等过程,主要参与巨噬细胞衍生的泡沫细胞分化、细胞分裂的正向调节、上皮细胞增殖的正向调节、肽基酪氨酸磷酸化的正向调节、胶原蛋白分解过程等生物学过程。行KEGG通路富集分析,得到通路28条,涉及癌症通路、乙型肝炎、癌症中的蛋白多糖、骨质分化、HIF-1信号通路、TNF信号通路、Toll样受体信号传导途径等多种信号通路,且通路上基质金属蛋白酶、IL-6、IL-1β、STAT1等靶点重复出现率高。结论真武汤可能通过调控MMP1、MMP2、MMP9阻止对心肌细胞外基质结构的破坏作用,延缓心肌重塑;通过对IL-1β、IL-6等调控,抑制炎症反应,减少细胞凋亡,进而达到延缓慢性心力衰竭的发生发展。Objective To explore the underlying mechanism ofZhenwuDecoction against chronic heart failure(CHF).Methods The active components of medicinals of ZhenwuDecoction,targets of the components,and targets of the disease were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),GeneCards,GisGeNET,and Online Mendelian Inheritance in Man(OMIM).The common targets of thedisease and the decoction were screened out and the medicinal-component-target-disease networkand the protein-protein interaction(PPI)network were constructed to screen the key targets,followed by Gene Ontology(GO)term enrichmentand Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment of the key targets.Results A total of 18 targets of ZhenwuDecoctionagainst CHF were screened out.According to the PPI network,12 were key targets:IL-1β,PPARG,ALB,IL-6,HMOX1,MMP2,TGFB1,TP53,STAT1,MMP1,MMP9,and VEGFA.The key targets were mainly involved in the protein extracellular matrix,the molecular functions ofmetalloendopeptidase activity,cytokine activity,enzyme binding,and identical protein binding,and biological processes of macrophage-derived foam cell differentiation,positive regulation of cell division,positive regulation of epithelial cell proliferation,positive regulation of peptidyl tyrosine phosphorylation,and collagen catabolic process.They were involved in 28 KEGG pathways such as cancer pathway,hepatitis B,proteoglycan in cancer,bone differentiation,HIF-1 signaling pathway,TNF signaling pathway,and Toll-like receptor signaling pathway,andtargets such as matrix metalloproteinase,IL-6,IL-1β,and STAT1 frequently appeared on the pathways.Conclusion ZhenwuDecotion may inhibit the damage to extracellular matrix structure of the myocardiumby regulating MMP1,MMP2,and MMP9 and suppress inflammatory response and reduce apoptosis by regulating IL-1β and IL-6,thereby delayingthedevelopmentof CHF.

关 键 词：慢性心力衰竭 真武汤 网络药理学 

分 类 号：R285.6[医药卫生—中药学]