基于Meta分析桥接网络药理学小青龙汤治疗AECOPD疗效及作用机制

基于Meta分析和网络药理学,综合评价小青龙汤联合常规西医治疗慢阻肺急性加重期（AECOPD）的疗效,初步探讨其潜在作用机制。通过检索中国知网（CNKI）、万方（Wangfang）、维普（VIP）、PubMed、Cochrane Library、Web of Science等数据库,收集小青龙汤联合常规西医治疗AECOPD的随机对照试验,根据纳入和排除标准对所有文献进行筛选,采用RevMan 5.4 软件进行Meta分析;随后通过TCMSP数据库检索筛选小青龙汤活性成分及其对应靶点,绘制小青龙汤–化合物–靶基因网络,筛选关键化合物,在TTD数据库、GeneCards数据库、OMIM数据库、DrugBank数据库检索与COPD有关的靶点基因,然后利用Excel筛选化学成分靶点与疾病靶点的交集靶点,绘制韦恩图,将交集靶点导入String数据库构建PPI网络,将小青龙汤活性成分靶点与COPD共同靶点导入David 6.8数据库进行基因本体论（GO）分析和京都基因与基因组百科全书（KEGG）分析,取前20条KEGG通路绘制潜在靶点–通路网络图。利用生物信息学技术进行分析,初步探讨其作用机制。Meta分析共纳入文献 34 篇,2 948例患者,结果显示小青龙汤联合常规西医治疗在总有效率、肺功能、动脉血气分析、中医症候总积分与中医症状体征评分、主要症状缓解时间、炎症因子水平等指标上均优于单用常规西医治疗。网络药理学共得到157种成分、150个共有靶点与130条相关通路,主要涉及HIF-1信号通路、肿瘤坏死因子信号通路、PI3K-Akt信号通路、Toll样受体信号通路等,涉及到氧化反应、炎症反应等主要生物过程。得出小青龙汤联合常规西医治疗在临床疗效上优于单用常规西医治疗方案,其潜在作用机制可能是通过抗炎、抗氧化应激过程来达到治疗AECOPD的目的。

The Efficacy and Mechanism of Xiaoqinglong Decoction in the Treatment of AECOPD based on Meta-analysis and Bridging Network Pharmacology

This study comprehensively evaluates the efficacy of Xiaoqinglong decoction combined with conventional treatment in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) based on Meta-analysis and network pharmacology, and preliminarily explores its potential action mechanism. Xiaoqinglong decoction combined with conventional treatment of randomized controlled trials for the treatment of AECOPD were collected by searching databases such as CNKI, Wanfang, VIP, PubMed, Cochrane Library and Web of Science; All literatures were screened based on inclusion and exclusion criteria and RevMan 5.4 software was used for Meta-analysis. The following steps were performed: The active components and their corresponding targets of Xiaoqinglong Decoction were searched and screened through tcmsp database; the Xiaoqinglong decoction compound target gene network was drawn; the key compounds were screened; the target genes related to COPD were searched in TTD database, genecards database, OMIM database and drugbank database; the intersection targets of chemical component targets and disease targets were screened by Excel, and the Wayne diagram was drawn; the intersection targets were imported into the string database to construct the PPI network and then the active ingredient targets of Xiaoqinglong decoction and the common targets of COPD were imported into the David 6.8 database for gene ontology (go) analysis and Kyoto Encyclopedia of genes and genomes (KEGG) analysis. The first 20 KEGG pathways were taken to draw the potential target pathway network diagram. Bioinformatics technology was used to analyze and preliminarily explore its mechanism. Meta-analysis included 34 articles and 2 948 patients totally. The results showed that Xiaoqinglong decoction combined with conventional treatment is superior to conventional treatment alone in terms of total effective rate, pulmonary function, arterial blood gas analysis, total score of TCM symptoms and signs, remission time of main symptoms and level of inflammatory factors. Network pharmacology has 157 components, 150 common targets and 130 related pathways, mainly involving HIF-1 signaling pathway, tumor necrosis factor signaling pathway, PI3K Akt signaling pathway, toll like receptor signaling pathway and other pathways, as well as major biological processes such as oxidation reaction and inflammatory reaction. Xiaoqinglong decoction combined with conventional western medicine is superior to conventional western medicine alone in clinical efficacy. Its potential mechanism may be to achieve the purpose of treating AECOPD through the process of anti-inflammatory and antioxidant stress.