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目的基于入血成分探讨开痹补肺汤治疗病毒性肺炎急性呼吸窘迫综合征（Acute respiratory distress syndrome, ARDS）的药效物质基础及潜在作用机制。方法 采用超高效液相色谱-四级杆-静电场轨道阱质谱（UHPLC-Q-Orbitrap-MS）技术分析小鼠灌胃开痹补肺汤后的入血成分。运用网络药理学方法，预测入血成分的作用靶点，并与病毒性肺炎ARDS疾病靶点进行交集分析，构建蛋白互作（PPI）网络，进行基因本体（GO）功能与京都基因与基因组百科全书（KEGG）通路富集分析。通过甲型流感病毒（PR8株）滴鼻感染C57BL/6J小鼠建立病毒性肺炎ARDS模型，评估开痹补肺汤对小鼠肺指数、肺组织病理损伤、血清炎症因子（TNF-α、IL-6、IL-1β、CXCL10）水平及肺组织NF-κB p65蛋白表达的影响。结果 共鉴定出58个开痹补肺汤入血成分。网络药理学筛选出86个药物-疾病交集靶点，GO和KEGG富集分析表明这些靶点显著富集于炎症反应、免疫调节等生物过程，其中NF-κB信号通路是关键通路。动物实验证实，开痹补肺汤能显著降低模型小鼠的肺指数，减轻肺泡结构破坏和炎细胞浸润，抑制血清中TNF-α、IL-6和CXCL10的升高，并下调肺组织中NF-κB p65的蛋白表达水平。结论 开痹补肺汤可能通过其多种入血成分，协同作用于NF-κB信号通路等关键靶点，抑制过度炎症反应，从而发挥治疗病毒性肺炎ARDS的作用。
Abstract：Objective To investigate the pharmacodynamic material basis and potential mechanism of Kaibi Bufei Decoction(KBD) in the treatment of viral pneumonia associated acute respiratory distress syndrome(ARDS) based on its blood-absorbed components.Methods Blood-absorbed components of KBD following oral administration in mice were identified using ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry(UHPLC-Q-Orbitrap-MS). Network pharmacology approaches were applied to predict the potential targets of these components. Shared targets between KBD and viral pneumonia associated ARDS were identified, and a protein-protein interaction(PPI) network was constructed. Gene Ontology(GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analyses were subsequently performed. A viral pneumonia– induced ARDS model was established in C57 BL/6J mice via intranasal infection with influenza A virus(PR8 strain). The effects of KBD on lung index, histopathological lung injury, serum inflammatory cytokine levels(TNF-α, IL-6, IL-1β, and CXCL10), and NF-κB p65 protein expression in lung tissue were evaluated.Results A total of 58 blood-absorbed components of KBD were identified. Network pharmacology analysis revealed 86 shared targets between KBD and viral pneumonia associated ARDS. GO and KEGG enrichment analyses indicated that these targets were significantly involved in biological processes related to inflammatory responses and immune regulation, with the NF-κB signaling pathway identified as a core pathway. In vivo experiments demonstrated that KBD significantly reduced the lung index in model mice, attenuated alveolar structural damage and inflammatory cell infiltration, suppressed the elevated serum levels of TNF-α, IL-6, and CXCL10, and downregulated NF-κB p65 protein expression in lung tissue. Conclusion Kaibi Bufei Decoction may exert its therapeutic effects against viral pneumonia associated ARDS through the synergistic action of multiple blood-absorbed components on multiple targets, particularly by modulating the NF-κB signaling pathway to suppress excessive inflammatory responses.
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基本信息:
DOI：10.13242/j.cnki.bingduxuebao.250336
中图分类号:R285.5
引用信息:
[1]薛贝,王明哲,张娜,等.基于入血成分探讨开痹补肺汤治疗病毒性肺炎ARDS的作用机制[J].病毒学报,2026,42(01):85-100.DOI:10.13242/j.cnki.bingduxuebao.250336.
基金信息:
2024科技创新专项（项目号：DZMKJCX-2024-012）,题目：从状态辨治出发探索有形无形之气双补治疗急性呼吸窘迫综合征的大动物模型建立及相关机制研究; 北京中医药大学东直门医院临床研究和成果转化能力提升试点项目面上专项（项目号：DZMG-MSZX-24005）,题目：开痹补肺汤联合正压通气通过嘧啶代谢通路调控中性粒细胞外陷阱在ARDS治疗中的临床研究~~