基于复杂网络的温心方治疗冠状动脉狭窄机制研究
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摘要
目的采用复杂网络方法探究温心方治疗冠状动脉狭窄的作用机制,为中药新药研发提供参考。方法利用多种中医药知识、药物靶点、疾病靶点数据库筛选温心方有效成分,构建温心方成分-靶点网络及冠状动脉狭窄疾病-靶点网络,采用Cytoscape软件整合并构建成分-疾病-靶点蛋白质相互作用(PPI)网络,对该网络进行拓扑分析及核心靶点筛选,然后进行生物过程及信号通路的富集分析。结果温心方含148种药物成分,可作用于226个靶点基因,冠状动脉狭窄共计471个疾病靶点,其中66个与温心方作用靶点重合。PPI网络及拓扑分析显示,温心方作用于冠状动脉狭窄的核心靶点380个,涉及ErbB信号通路、B细胞抗原受体信号通路、HIF-1信号通路、TGF-β信号通路、凝血活动、G1/S细胞周期转换、Wnt信号通路等多种生物过程及信号通路。结论温心方治疗冠状动脉狭窄多靶点、多途径的作用网络,提示其可能通过抗凋亡、调控细胞周期、抗炎、抗凝、促血管新生、保护内皮细胞发挥治疗作用。
Objective To explore the mechanism of Wenxin Decoction in treating coronary artery stenosis based on complex network method; To provide references for drug development. Methods Active ingredients in Wenxin Decoction were screened by using a variety of TCM knowledge, drug targets, and disease target databases, and Wenxin Decoction component-target network and coronary stenosis-target network were constructed. Cytoscape software was used to integrate and construct a component-disease-target protein-protein interaction(PPI) network,and the network was under topological analysis and core target screening. Enrichment analysis of biological processes and signaling pathways were conducted. Results A total of 148 ingredients in Wenxin Decoction were found to act on226 target genes. Coronary artery stenosis had a total of 471 disease targets, of which 66 coincided with Wenxin Decoction targets. PPI network and topological analysis showed that Wenxin Decoction acted on 380 core targets of coronary stenosis, involving various biological processes and signaling pathways such as ErbB signaling pathway, B cell antigen receptor signaling pathway, HIF-1 signaling pathway, TGF-β signaling pathway, clotting activity, G1/S cell cycle transition and Wnt signaling pathway. Conclusion The multi-target and multi-path network of Wenxin Decoction for treating coronary artery stenosis implies that it may play a therapeutic role through anti-apoptosis,regulation of cell cycle, anti-inflammatory, anticoagulation, angiogenesis, and protection of endothelial cells.
Objective To explore the mechanism of Wenxin Decoction in treating coronary artery stenosis based on complex network method; To provide references for drug development. Methods Active ingredients in Wenxin Decoction were screened by using a variety of TCM knowledge, drug targets, and disease target databases, and Wenxin Decoction component-target network and coronary stenosis-target network were constructed. Cytoscape software was used to integrate and construct a component-disease-target protein-protein interaction(PPI) network,and the network was under topological analysis and core target screening. Enrichment analysis of biological processes and signaling pathways were conducted. Results A total of 148 ingredients in Wenxin Decoction were found to act on226 target genes. Coronary artery stenosis had a total of 471 disease targets, of which 66 coincided with Wenxin Decoction targets. PPI network and topological analysis showed that Wenxin Decoction acted on 380 core targets of coronary stenosis, involving various biological processes and signaling pathways such as ErbB signaling pathway, B cell antigen receptor signaling pathway, HIF-1 signaling pathway, TGF-β signaling pathway, clotting activity, G1/S cell cycle transition and Wnt signaling pathway. Conclusion The multi-target and multi-path network of Wenxin Decoction for treating coronary artery stenosis implies that it may play a therapeutic role through anti-apoptosis,regulation of cell cycle, anti-inflammatory, anticoagulation, angiogenesis, and protection of endothelial cells.
引文
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[20]张明雪,曹洪欣.温阳活血化痰法降低冠心病心阳虚证血小板聚集率的机制探讨[J].中国中西医结合急救杂志,2003,10(2):84-86.
[21]张明雪,曹洪欣.温心胶囊对冠心病心阳虚证大鼠血小板功能的影响[J].中国急救医学,2002,22(10):563-564.
[22]沈雁,曹洪欣,周景华,等.实验性心力衰竭大鼠心肌细胞细胞间黏附分子1的表达[J].中国临床康复,2005,9(39):30-32.
[23]冯玲,曹洪欣,胡元会,等.温阳益心方对大鼠心悸梗死模型心脏促血管新生的机制研究[J].中国中医基础医学杂志,2009,15(4):274-276.
[2]曹洪欣,张华敏.痰瘀互结与冠心病发病机理辨识[J].中医药学刊,2001,19(6):544-545.
[3]曹洪欣,殷惠军,张腾.温心胶囊抗动脉粥样硬化的形态学研究[J].中国中医药科技,2001,8(1):39.
[4]李同达.温阳益心活血化痰法对冠状动脉粥样硬化大鼠血管内皮保护作用研究[D].北京:中国中医科学院,2014.
[5]WANG J,LI X J.Drug targets discovery based on dynamic signal transduction networks[J].Acta Pharm Sin,2010,45(1):1-8.
[6]BARABáSI A L,GULBAHCE N,LOSCALZO J.Network medicine:a network-based approach to human disease[J].Nat Rev Genet,2011,12(1):56-68.
[7]LI J,ZHAO P,LI Y,et al.Systems pharmacology-based dissection of mechanisms of Chinese medicinal formula Bufei Yishen as an effective treatment for chronic obstructive pulmonary disease[J].Sci Rep,2015,5(10):15290.
[8]WANG X,WANG Q,ZHANG A,et al.Metabolomics study of intervention effects of Wen-Xin-Formula using ultra highperformance liquid chromatography/mass spectrometry coupled with pattern recognition approach[J].J Pharm Biomed Anal,2013,74(2):22-30.
[9]WANG S L,WANG H B,LU Y.Tianfoshen oral liquid:a CFDA approved clinical traditional chinese medicine,normalizes major cellular pathways disordered during colorectal carcinogenesis[J].Oncotarget,2017,8(9):14549-14569.
[10]BARABáSI A L,OLTVAI Z N.Network biology:understanding the cell’s functional organization[J].Nat Rev Genet,2004,5(2):101-113.
[11]HOPKINS A L.Network pharmacology[J].Nat Biotechnol,2007,25:1110-1111.
[12]向铮,蔡小军,曾苏.基于复杂网络与代谢组学的中药药代动力学研究思考与探讨[J].药学学报,2012,47(5):558-564.
[13]李从林,王博龙.基于网络药理学的益母草作用机制分析[J].中国中医药信息杂志,2018,25(12):102-106.
[14]魏金婷,刘文奇.植物药活性成分β-谷甾醇研究概况[J].莆田学院学报,2007,14(2):38-40,46.
[15]王敏,刘保林,国旭丹.槲皮素及其代谢物抑制氧化应激与炎症[J].食品科学,2013,34(15):256-260.
[16]张腾,曹洪欣,盛小禹,等.温心胶囊对大鼠实验性缺血心肌细胞凋亡及Bcl-2、Fas蛋白表达的影响[J].中国中西医结合杂志,2003,23(10):769-771.
[17]唐丹丽,曹洪欣,张华敏.温阳益心法对动脉粥样硬化大鼠主动脉MCP-I、NF-kB表达的影响[J].中国中医基础医学杂志,2007,13(2):110-112.
[18]唐丹丽,曹洪欣,张华敏.温阳益心法对动脉粥样硬化大鼠血清C反应蛋白和白细胞介素-6水平的影响[J].中国中医药信息杂志,2007,14(7):29-30.
[19]张明雪,曹洪欣.温心胶囊对冠心病心阳虚证大鼠血小板形态MPV,PDW值的影响[J].中药新药与临床药理,2005,16(1):30-33.
[20]张明雪,曹洪欣.温阳活血化痰法降低冠心病心阳虚证血小板聚集率的机制探讨[J].中国中西医结合急救杂志,2003,10(2):84-86.
[21]张明雪,曹洪欣.温心胶囊对冠心病心阳虚证大鼠血小板功能的影响[J].中国急救医学,2002,22(10):563-564.
[22]沈雁,曹洪欣,周景华,等.实验性心力衰竭大鼠心肌细胞细胞间黏附分子1的表达[J].中国临床康复,2005,9(39):30-32.
[23]冯玲,曹洪欣,胡元会,等.温阳益心方对大鼠心悸梗死模型心脏促血管新生的机制研究[J].中国中医基础医学杂志,2009,15(4):274-276.