基于网络药理学的银翘散合桑菊饮加减方、麻杏石甘汤加减方与抗病毒西药作用机制比较——以2018初冬流行性感冒轻症为例
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摘要
目的分析中药方剂与抗病毒西药治疗流感轻症的机制差异,探讨中药复方抗流感病毒的可能机制。方法选取银翘散合桑菊饮加减方、麻杏石甘汤加减方,与奥司他韦、扎那米韦、帕拉米韦作对比。在SymMap等生物数据库中分别检索两中药复方中药物的靶蛋白,与疾病基因库中流感的疾病基因进行匹配。利用String数据库及Cytoscape软件对靶蛋白进行互作关系和拓扑分析,运用DAVID数据库对两中药复方得分高的模块进行富集分析,明确两中药复方治疗流感轻症的生物机制。结果纳入的3个西药的靶蛋白均为神经氨酸酶,KEGG通路均涉及糖降解过程。银翘散合桑菊饮加减方的靶蛋白中涉及流感基因436个、生物进程261个、KEGG通路125个;麻杏石甘汤加减方的靶蛋白中涉及流感基因464个、生物进程262个、KEGG通路115个。除共同涉及的大量流感基因与信号通路外,银翘散合桑菊饮加减方涉及基因SIRT1、CAT和Th17细胞分化、T细胞受体信号通路、神经营养素信号通路;麻杏石甘汤加减方涉及基因CDKN1B、LEP。结论与抗病毒西药相比,两个中药复方通过多靶标、多通路调节人体,其功能更集中于提高人体的免疫能力,促进宿主自身抗感染能力。
Objective To analyze the difference of mechanism between traditional Chinese medicine(TCM) prescription and antiviral western medicine in the treatment of mild influenza,and to explore the possible mechanism of TCM compound anti-influenza virus. Methods Yinqiao Powder(银翘散) combined Modified Sangju Decoction(桑菊饮) and Modified Maxing Shigan Decoction(麻杏石甘汤) were selected to compare with oseltamivir,zanamivir and peramivir. In the biological database such as Sym Map,the target proteins of the drugs in the two TCM prescriptions were respectively searched,and the disease genes of the influenza in the disease gene pool were matched. The String database and Cytoscape software was used to interact and topologically analyze the target proteins,and the DAVID database was used to conduct enrichment analysis of the modules with high scores of the two TCM prescriptions,so as to clarify the biological mechanism of the two TCM compounds in the treatment of influenza mild disease. Results The target proteins of the included 3 western medicines were all neuraminidase,and the KEGG pathway involved sugar degradation process. There were 436 influenza genes,261 biological processes and 125 KEGG pathways in the target protein of Yinqiao Powder combined Modified Sangju Decoction. The target protein of Modified Maxing Shigan Decoction involved 464 influenza genes,262 biological processes,and 115 KEGG pathways. Except for a large number of same genes and signaling pathways,Yinqiao Powder combined Modified Sangju Decoction had the unique genes SIRT1,CAT and Th17 cell differentiation,T cell receptor signaling pathway and neurotrophin signaling pathway; Modified Maxing Shigan Decoction only had the unique genes CDKN1 B,LEP. Conclusion Compared with antiviral western medicine,the two TCM prescriptions regulate the human body through multi-target and multi-channel,and its function is more focused on improving the immunity of the human body and promoting the host's own anti-infective ability.
Objective To analyze the difference of mechanism between traditional Chinese medicine(TCM) prescription and antiviral western medicine in the treatment of mild influenza,and to explore the possible mechanism of TCM compound anti-influenza virus. Methods Yinqiao Powder(银翘散) combined Modified Sangju Decoction(桑菊饮) and Modified Maxing Shigan Decoction(麻杏石甘汤) were selected to compare with oseltamivir,zanamivir and peramivir. In the biological database such as Sym Map,the target proteins of the drugs in the two TCM prescriptions were respectively searched,and the disease genes of the influenza in the disease gene pool were matched. The String database and Cytoscape software was used to interact and topologically analyze the target proteins,and the DAVID database was used to conduct enrichment analysis of the modules with high scores of the two TCM prescriptions,so as to clarify the biological mechanism of the two TCM compounds in the treatment of influenza mild disease. Results The target proteins of the included 3 western medicines were all neuraminidase,and the KEGG pathway involved sugar degradation process. There were 436 influenza genes,261 biological processes and 125 KEGG pathways in the target protein of Yinqiao Powder combined Modified Sangju Decoction. The target protein of Modified Maxing Shigan Decoction involved 464 influenza genes,262 biological processes,and 115 KEGG pathways. Except for a large number of same genes and signaling pathways,Yinqiao Powder combined Modified Sangju Decoction had the unique genes SIRT1,CAT and Th17 cell differentiation,T cell receptor signaling pathway and neurotrophin signaling pathway; Modified Maxing Shigan Decoction only had the unique genes CDKN1 B,LEP. Conclusion Compared with antiviral western medicine,the two TCM prescriptions regulate the human body through multi-target and multi-channel,and its function is more focused on improving the immunity of the human body and promoting the host's own anti-infective ability.
引文
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[2]王玉光,谷晓红,马家驹,等.2017-2018年北京地区流行性感冒病证特征及应对策略[J].北京中医药,2018,37(1):3-7.
[3]国家卫生和计划生育委员会.流行性感冒诊疗方案(2018年版)[J].中国感染控制杂志,2018,17(2):181-184.
[4]EHRHARDT C,SEYER R,HRINCIUS ER,et al.Interplay between influenza A virus and the innate immune signaling[J].Microbes Infect,2010,12(1):81-87.
[5]HALE BG,ALBRECHT RA,GARCA-SASTRE A.Innate immune evasion strategies of influenza viruses[J].Future Microbiol,2010,5(1):23-41.
[6]LUDWIG S.Targeting cell signalling pathways to fight the flu:Towards a paradigm change in anti-influenza therapy[J].J Antimicrob Chemoth,2009,64(1):1-4.
[7]张建国,张继宁,黄勋娟.神经氨酸酶抑制剂的研究进展[J].化学与生物工程,2014,31(4):1-5,23.
[8]程能能,陈斌艳,王永铭.新型口服抗流感药:奥司他韦[J].中国临床药学杂志,2002,11(1):55-59.
[9]卞家蓉,修清玉.神经氨酸酶抑制剂扎那米韦的药理作用与临床应用[J].中国新药与临床杂志,2013,32(8):614-618.
[10]赵丽嘉,王利华,胡雅萍,等.A/B型流感病毒治疗药物:帕拉米韦水合物(Peramivir hydrate)[J].药物评价研究,2010,33(5):400-406.
[11]JEON,SW,HAN C.Psychiatric symptoms in a patient with influenza A(H1N1)treated with oseltamivir(Tamiflu):a case report[J].Clin Psychopharm NEU,2015,13(2):209-211.
[12]陈腾飞,刘清泉.谈中医药对于2017-2018年冬季流感的防治思路:《流行性感冒诊疗方案(2018版)》中医解读[J].世界中医药,2018,13(2):271-273,277.
[13]HERS I,VINCENT EE,TAVAR JM.Akt signalling in health and disease[J].Cell Signal,2011,23(10):1515-1527.
[14]DENT P,YACOUB A,FISHER PB,et al.MAPK pathways in radiation responses[J].Oncogene,2003,22(37):5885-5896.
[15]KAWAI T,AKIRA S.TLR signaling[J].Semin Immunol,2007,19(1):24-32.
[16]STROBER W,MURRAY PJ,KITANI A,et al.Signalling pathways and molecular interactions of NOD1 and NOD2[J].Nature Rev Immunol,2006,6(1):9-20.
[17]HONG WG,PYO JS.The clinicopathological significance of SIRT1 expression in colon cancer:An immunohistochemical study and meta-analysis[J].Pathol Res Pract,2018,214(10):1550-1555.
[18]GAETANI GF,FERRARIS AM,ROLFO M,et al.Predominant role of catalase in the disposal of hydrogen peroxide within human erythrocytesp[J].Blood,1996,87(4):1595-1599.
[19]POLYAK K,LEE MH,ERDJUMENT-BROMAGE H,et al.Cloning of p27Kip1,a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals[J].Cell,1994,78(1):59-66.
[20]WABITSCH M,JENSEN PB,BLUM WF,et al.Insulin and cortisol promote leptin production in cultured human fat cells[J].Diabetes,1996,45(10):1435-1438.