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目的:运用网络药理学探讨补阳还五汤治疗肺纤维化的作用机制,并运用Meta分析进一步验证临床疗效。方法:在中药系统药理学数据库与分析平台(TCMSP)及上海有机所化学数据库检索成分靶点,在基因卡片(GeneCards)、人类孟德尔遗传数据库(OMIM)、药物银行(DRUGBANK)数据库获得特发性肺纤维化的疾病靶点,应用String网构建蛋白质与蛋白质相互作用(PPI)网络,采用Metascape进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。检索中国知网(CNKI)等7个中英文数据库,纳入7项随机对照研究,采用RevMan 5.3进行Meta分析。结果:网络药理学筛选得到补阳还五汤有效活性成分132个、作用靶点241个、疾病靶点1088个,取交集得靶点76个,PPI分析发现关键靶点涉及IL6、TNF、VEGFA等。富集分析得到GO条目1470条(P<0.01);KEGG富集得到181条通路(P<0.01)。Meta分析纳入412例患者,分析显示补阳还五汤可提高临床总有效率(RR=1.38,95%CI[1.23,1.56],P<0.00001)和动脉血氧分压水平(MD=5.53,95%CI[3.59,7.47],P<0.00001),且补阳还五汤未增加不良事件发生率(RR=0.43,95%CI[0.18,1.04],P=0.06)。结论:补阳还五汤治疗肺纤维化具有多成分、多靶点、多通路的特点,Meta分析证实其具有潜在疗效。
Abstract：s Objective:To explore the mechanism of Buyang Huanwu Decoction（补阳还五汤） in the treatment of pulmonary fibrosis by using network pharmacology,and to further verify the clinical efficacy by using Meta-analysis. Methods:Component targets were retrieved from TCMSP database and Chemical Database of Shanghai Institute of Organic Chemistry,disease targets of idiopathic pulmonary fibrosis were obtained from GeneCards,OMIM and DRUGBANK database,PPI network was constructed by String network,and GO and KEGG analysis was performed by Metascape.Seven Chinese and English databases including CNKI were searched,and 7 randomized controlled trial were included. Meta-analysis was performed by RevMan 5.3. Results:A total of 132 active ingredients,241 action targets and 1088 disease targets were ob tained by network pharmacologic screening,and 76 targets were obtained from intersection. PPI analysis showed that the key targets involved IL6,TNF and VEGFA. Enrichment analysis yielded 1470 GO entries(P<0.01). KEGG enrichment yielded 181 pathways(P<0.01). Meta-analysis of 412 patients showed that Buyang Huanwu Decoction could improve the total clinical response rate(RR= 1.38,95%CI[1.23,1.56],P<0.00001) and arterial partial pressure of oxygen(MD= 5.53,95%CI[3.59,7.47],P<0.00001). Buyang Huanwu Decoction did not increase the incidence of adverse events(RR= 0.43,95%CI[0.18,1.04],P= 0.06). Conclusions:Buyang Huanwu Decoction has the characteristics of multiple components,multiple targets and multiple pathways in the treatment of pulmonary fibrosis. Meta-analysis confirmed its potential curative effect.
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基本信息:
DOI：10.16295/j.cnki.0257-358x.2022.02.006
中图分类号:R285
引用信息:
[1]韩烁,孟昭阳,刘骅漫,等.基于网络药理学和Meta分析探讨补阳还五汤治疗特发性肺纤维化作用机制[J],2022,41(02):161-170.DOI:10.16295/j.cnki.0257-358x.2022.02.006.
基金信息:
国家自然科学基金青年项目（编号：81804034;82004285）;; 山东省医药卫生科技发展计划项目（编号：2017WSB23008）