基于网络药理学的血必净治疗H1N1病毒引起的肺微血管渗漏的潜在机制

韩甜甜 李丹华 刘小虹 詹少峰 江勇

摘要 目的：探讨血必净注射液干预肺微血管渗漏辅助治疗H1N1病毒性肺炎的潜在药理作用机制。方法：收集血必净注射液中的活性成分，反向预测潜在作用靶点。从GeneCards数据库中获得疾病相关靶点。使用Venny工具对药物及疾病的潜在靶点进行交集分析，并对交集靶点进行蛋白质-蛋白质相互作用（PPI）网络的构建。利用DAVID和京都基因和基因组百科全书（KEGG）数据库进行通路注释，采用Cytoscape软件构建“中药-活性成分-靶点-疾病”网络模型。结果：共筛选出25个活性分子，通过调控TP53、VEGFA、EGFR、TNF、TLR4、CASP3、JUN等关键基因，影响核因子κB信号通路、HIF-1信号通路、T细胞受体信号通路、细胞凋亡信号转导途径、血管内皮生长因子信号通路和Toll样受体信号转导途径等91条通路发挥抗炎、调节免疫等作用。结论：本研究明确了血必净注射液抗炎和调节免疫作用的物质基础，为进一步阐释血必净注射液干预肺微血管渗漏辅助治疗H1N1病毒性肺炎相关机制提供科学依据。

关键词 血必净注射液;H1N1病毒;肺微血管渗漏;内皮细胞;潜在机制;内皮屏障;网络药理学;病毒性肺炎

Abstract Objective：To explore the potential pharmacological mechanism of Xuebijing injection in the intervention of pulmonary microvascular leakage in the adjuvant treatment of H1N1 viral pneumonia.Methods：Active ingredients in Xuebijing injection were collected，and the potential targets were prediected.Disease-related targets were obtained from the Genecards database.The Venny tool was used to analyze the intersection of potential targets of drugs and diseases，and a PPI network for the intersection targets was constructed.DAVID and KEGG databases were retrieved for pathway annotation，using Cytoscape software to construct a network model of “Chinese medicine-active ingredients-targets-disease”.Results：A total of 25 active molecules were screened out，which can regulate key genes of TP53、VEGFA、EGFR、TNF、TLR4、CASP3 and JUN to affect 91 pathways，including the NF-κB signaling pathway，HIF-1 signaling pathway，and TTR，apoptosis signaling pathway，vascular endothelial growth factor signaling pathway，and Toll-like receptor signaling pathway，with anti-inflammatory and immune regulation functions.Conclusion：This study clarifies the material basis of Xuebijing injection′s anti-inflammatory and immune regulation effects，and provides a scientific basis for further elucidating the mechanism of Xuebijing injection′s intervention in pulmonary microvascular leakage adjuvant treatment of H1N1 viral pneumonia.

Keywords Xuebijing injection; H1N1; Pulmonary microvascular leakage; Endothelial cells; Potential mechanism; Endothelial barrier; Network pharmacology; Viral pneumonia

中圖分类号：R285.5文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.22.006

自1918年西班牙流感大流行以来，流感病毒感染一直是全球健康关注的问题[1]。2009年由一种新型的甲型H1N1流感病毒引起“墨西哥流感大流行”，波及全球214个国家和地区，死亡人数超过290 000人，其中201 000人死于呼吸衰竭[2]。H1N1病毒扩散到下呼吸道，则会导致病毒性肺炎，进而可发展为急性呼吸窘迫综合征（Acute Respiratory Distress Syndrome，ARDS）以及急性肺损伤（Acute Lung Injury，ALI），即肺微血管渗漏增加导致肺水肿、低氧血症和呼吸衰竭的综合征[3]。……