张平安 高娜 陈明哲 张莹雪 李奕璇 吴建军

摘要 目的：利用网络药理学分析小青龙汤治疗慢性阻塞性肺疾病（COPD）的作用机制。方法：在中药系统药理学数据库与分析平台（TCMSP）检索小青龙汤药物活性成分和靶点，绘制中药-化合物-靶基因网络，筛选关键化合物;利用GeneCards和人类孟德尔遗传数据库（OMIM）搜索COPD疾病基因;绘制韦恩图并获取药物-疾病共同基因;利用小青龙汤-慢阻肺药物疾病共同基因绘制蛋白质-蛋白质相互作用（PPI）网络，根据网络关系选择核心基因;对核心基因分别进行基因本体（GO）功能注释和富集分析和京都基因和基因组百科全书（KEGG）通路富集分析。结果：挖掘得到小青龙汤中药活性成分137个，潜在作用靶点188个，慢性阻塞性肺疾病相关靶点6 949个，小青龙汤-COPD共同靶点160个，主要富集于92个生物过程和49条信号通路上。结论：小青龙汤中多个药物含有山柰酚、槲皮素、（+）-儿茶素、豆甾醇、β-谷固醇等成分，可作用于AKT1、IL6、MAPK1、PTGS2、TP53等核心基因，调控氧化应激反应、血小板α-颗粒等生物过程，参与HIF-1、PI3K-AKT信号通路的调节，干预氧化应激反应和炎症反应等过程，产生抑制炎症反应、抗氧化应激的作用，进而通过上述过程参与COPD的炎症反应与氧化应激过程。

关键词 网络药理学;小青龙汤;慢性阻塞性肺疾病;靶基因;GO功能注释;KEGG通路富集分析;炎症反应;氧化应激

Abstract Objective：to analyze the mechanism of Xiaoqinglong Decoction in the treatment of chronic obstructive pulmonary disease（COPD） by network pharmacology.Methods：the active ingredients and targets of Xiaoqinglong Decoction were searched in TCMSP database platform，and the traditional Chinese medicine compound target gene network was drawn to screen the key compounds; the COPD disease genes were searched by genecards and OMIM database; the Wayne map was drawn to obtain the drug disease common gene; the PPI protein interaction network was drawn by Xiaoqinglong Decoction COPD drug disease common gene Go functional annotation and KEGG pathway enrichment analysis were performed on the core genes.Results：137 active components of Xiaoqinglong decoction，188 potential targets，6949 targets related to COPD and 160 common targets of Xiaoqinglong Decoction COPD were obtained，which were mainly enriched in 92 biological processes and 49 signal pathways.Conclusion：Many drugs in Xiaoqinglong Decoction contain kaempferol，quercetin，（+）-catechin，stigmasterol，β-sitosterol and other components，which can act on AKT1，IL6，mapk1，PTGS2，TP53 and other core genes，regulate oxidative stress response，platelet α-granule and other biological processes，participate in the regulation of HIF-1，PI3K Akt signaling pathway，intervene in oxidative stress response and inflammatory response，and produce high yield Through the above process，it participates in the inflammatory reaction and oxidative stress process of COPD.

Keywords Network pharmacology; Xiaoqinglong Decoction; Chronic obstructive pulmonary disease; Target gene; Go function annotation; KEGG pathway enrichment analysis; Inflammatory response; Oxidative stress

中圖分类号：R285文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.24.003

慢性阻塞性肺疾病（Chronic Obstructive Pulmoriary Disease，COPD）又称慢阻肺，是一种持续存在的慢性气道炎症疾病，以反复出现的呼吸道症状和不可逆转的气流受限为特征，发作期外周气道和肺实质的中性粒细胞和巨噬细胞以及包括Tc1和ILC3淋巴细胞等炎症细胞的数量明显增加，其释放的诸多炎症介质也与疾病密切相关[1]。……