基于网络药理学和分子对接探讨丹参治疗术后腹腔粘连的作用机制
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篇名: 基于网络药理学和分子对接探讨丹参治疗术后腹腔粘连的作用机制
TITLE: Investigation on the Mechanism of Salvia miltiorrhiza in the Treatment of Postoperative Abdominal Adhesion Based on Network Pharmacology and Molecular Docking
摘要: 目的:探讨丹参治疗术后腹腔粘连(PAA)的潜在作用机制。方法:利用中药系统药理学分析平台(TCMSP)、Swiss-ADME、Perl、UniProt等数据库检索丹参活性成分及其靶点基因,利用GeneCards、在线人类孟德尔遗传数据库(OMIM)、PubMed数据库检索与PAA相关的靶点基因。利用生物信息学在线数据库作图工具绘制维恩(Venn)图,筛选活性成分-PAA的交叉靶点。利用STRING平台构建活性成分-PAA相关靶点网络、交叉靶点的蛋白互作(PPI)网络等,并筛选枢纽基因。借助R3.6.1软件进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。以枢纽基因编码蛋白为受体、活性成分丹参酮ⅡA为配体,采用AutoDock1.5.6工具进行分子对接。结果:共得到38种高胃肠道吸收的丹参活性成分及其相应的72个靶点基因,以及755个与PAA相关的靶点基因。Venn图结果显示,丹参活性成分与PAA共有33个交叉靶点。丹参酮ⅡA、二氢丹参内酯等成分可能是活性成分-PAA相关靶点网络的重要节点,FOS、APP、ACHE、CASP3、PTGS2可能是交叉靶点PPI网络的枢纽基因。GO富集结果表明,交叉靶点主要富集于肾上腺素受体活性、儿茶酚胺结合、G蛋白偶联胺受体活性等;KEGG通路富集分析表明,交叉靶点主要富集于神经活性配体-受体相互作用、环磷酸鸟苷酸依赖的蛋白激酶、内分泌抵抗、表皮生长因子受体酪氨酸激酶抑制剂抵抗和钙信号通路等。分子对接分析表明,丹参酮ⅡA可与原癌基因蛋白c-Fos、淀粉样前体蛋白、乙酰胆碱酯酶、胱天蛋白酶3和前列腺素G/H合酶2上VAL-580等多个氨基酸残基形成氢键。结论:丹参活性成分可能通过直接或间接作用于神经活性配体-受体相互作用、环磷酸鸟苷酸依赖的蛋白激酶、内分泌抵抗、表皮生长因子受体酪氨酸激酶抑制剂抵抗和钙信号通路等途径来发挥治疗PAA的作用。
ABSTRACT: OBJECTIVE:To investigate the potential mechanism of Salvia miltiorrhiza in the treatment of postoperative abdominal adhesion (PAA). METHODS :Active components and target genes of S. miltiorrhiza were retrieved from TCMSP database,SwissADME database ,Perl database ,UniProt database and other databases. GeneCards ,OMIM and PubMed database were used to retrieve target genes related to PAA. Venn diagram was drawn by using mapping tool of bioinformatic online database so as to screen the intersecting targets of active component-PAA. STRING platform was adopted to establish target network related to active component-PAA and protein-protein interaction (PPI)network of intersecting targets ,etc.,and to screen hub genes. Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genom es(KEGG)pathway enrichment were carried out by using R 3.6.1 software. Using the protein encoded by hub gene as receptor and tanshinone Ⅱ A as ligand ,the molecular docking was carried out with AutoDock 1.5.6 tool. RESULTS :A total of 38 active components of S. miltiorrhiza with high gastrointestinal absorption and their corresponding 72 targets,755 PAA-related target genes were identified. Results of Venn diagram showed that there were 33 intersecting targets of active components of chuqi90@163.com S. miltiorrhiza with PAA. Tanshinone ⅡA,dihydrotanshinolac- tone and other components may be important nodes of the target network related to active component-PAA. FOS,APP,ACHE, CASP3 and PTGS2 may be the hub genes in PPI network of intersecting targets. Results of GO enrichment showed that the intersecting targets were mainly concentrated in adrenergic receptor activity ,catecholamine binding ,G protein-coupled amine receptor activity and so on ;KEGG pathway enrichment analysis showed that the intersecting targets were mainly enriched in neuroactive ligand-receptor interaction ,cGMP-PKG signaling pathway ,endocrine resistance ,EGFR-tyrosine kinase inhibitor resistance and calcium signaling pathway.Molecular docking analysis showed that tanshinone ⅡA could form hydrogen bonds with many amino acid residues such as VAL- 580 of proto oncogenes c-Fos ,amyloid precursor protein ,acetylcholinesterase,caspase 3 and prostaglandin G/H synthase 2. CONCLUSIONS :The active components of S. miltiorrhiza play a role in the treatment of PAA by directly or indirectly acting on neuroactive ligand-receptor interaction ,cGMP-PKG signaling pathway ,endocrine resistance , EGFR-tyrosine kinase inhibitor resistance resistance and calcium signaling pathway.
期刊: 2021年第32卷第24期
作者: 刘文钦,吴馥凌,王龙,杨琴,吴江杰,侯连兵,唐斓,侯楚祺
AUTHORS: LIU Wenqin ,WU Fuling ,WANG Long,YANG Qin,WU Jiangjie ,HOU Lianbing ,TANG Lan,HOU Chuqi
关键字: 术后腹腔粘连;丹参;网络药理学;分子对接
KEYWORDS: Postoperative abdominal adhesion ;Salvia miltiorrhiza ;Network pharmacology ;Molecular docking
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