目的 采用网络药理学和多中心临床数据探讨清肺承气汤治疗腹腔感染所致急性呼吸窘迫综合征（acute respiratory distress syndrome，ARDS）的作用机制。方法 通过中药系统药理学分析平台（Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform，TCMSP）数据库检索清肺承气汤的化学成分和靶点。采用Cytoscape 3.7.1软件建立"化合物-靶点"网络、靶点间的蛋白相互作用（protein protein interaction，PPI）网络，并对预测靶点进行京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）富集分析。从3所医院选取27例腹腔感染所致ARDS患者，随机分为13例对照组和14例清肺承气汤组，分别于治疗前后3 d取肺泡灌洗液，微球检测法检测患者肺泡灌洗液中白细胞介素-4（interleukin 4，IL-4）、白细胞介素-6（interleukin 6，IL-6）、白细胞介素-10（interleukin 10，IL-10）水平；流式细胞术检测患者肺泡巨噬细胞的凋亡情况。结果 筛选得到清肺承气汤中78种活性成分，对应63个潜在靶点；"化合物-靶点"网络和PPI网络度值靠前的靶点为过氧化物酶体增殖物激活受体γ（peroxisome proliferators-activated receptor γ，PPARγ）、B细胞淋巴瘤/白血病-2（B-cell lymphoma-2，Bcl-2）、IL-6、IL-10、γ干扰素（interferon-gamma，INFG），化合物为槲皮素和木犀草素；潜在靶点的KEGG通路排序靠前的炎症相关通路为核因子-κB（nuclear factor-κB，NF-κB）通路、肿瘤坏死因子（tumor necrosis factor，TNF）信号通路、白细胞介素-17（interleukin 17，IL-17）通路、T细胞受体通路等信号通路。与对照组比较，清肺承气汤组患者肺泡灌洗液中IL-6水平显著升高（P<0.05），IL-10水平显著降低（P<0.05），肺泡巨噬细胞的凋亡面积显著降低（P<0.001）。结论 清肺承气汤中的有效成分可以通过IL-6、Bcl-2、IL-10、趋化因子配体2（CXC chemokine ligand 2，CXCL2）等靶点参与调控多条信号通路来影响IL-4、IL-6、IL-10分泌和细胞凋亡，从而治疗ARDS。

Objective To elucidate the underlying molecular mechanism of Qingfei Chengqi Decoction (清肺承气汤) in treatment of patients with acute respiratory distress syndrome (ARDS) caused by abdominal infection using network pharmacology and multi-center clinical data. Methods Through the database of Chinese Medicine System Pharmacology Analysis Platform (TCMSP), the chemical constituents and targets of Qingfei Chengqi Decoction was retrieved. Cytoscape 3.7.1 software was used to establish a "compound-target" network, a predicted protein-protein interaction (PPI) network between predicted targets, and a KEGG enrichment analysis of predicted targets. A total of 27 patients with ARDS due to celiac infection were selected from three hospitals and were randomly divided into Qingfei Chengqi Decoction group (14 cases) and control group (13 cases). Alveolar lavage fluid was taken 3 d before and after treatment; Levels of IL-4, IL-6, IL-10 were detected by microsphere detection; Alveolar macrophage apoptosis was analyzed by flow cytometry. Results A total of 78 active compounds and 63 potential targets of Qingfei Chengqi Decoction were screened. From "compound-target" network and PPI network, targets ranked the top were PPARγ, Bcl-2, IL-6, IL-10 and INFG; Compounds were quercetin and luteolin. Inflammatory pathways ranked higher in KEGG pathway analysis were NF-κB, TNF signaling pathway, IL-17 pathway and T cell receptor pathway. Compared with control group, level of IL-6 was significantly increased (P < 0.05), level of IL-10 was significantly decreased (P < 0.05), and apoptotic area of alveolar macrophages was significantly decreased (P < 0.001) in Qingfei Chengqi Decoction group. Conclusion Compounds in Qingfei Chengqi Decoction could regulate multiple signal pathways through targets such as IL-6, Bcl-2, IL-10, and CXCL2 to regulate the secretion of IL-4, IL-6, IL-10 and cell apoptosis to treat ARDS.

R285.6

天津市卫生行业重点攻关项目（15KG121）