南方医科大学学报2025，Vol.45Issue(7)：1409-1422,14.DOI:10.12122/j.issn.1673-4254.2025.07.07
益气滋肾方通过抑制PI3K/Akt/NF-κB通路改善小鼠慢性阻塞性肺疾病的炎症反应
Yiqi Zishen Formula ameliorates inflammation in mice with chronic obstructive pulmonary disease by inhibiting the PI3K/Akt/NF-κB signaling pathway
摘要
Abstract
Objective To investigate pharmacologically active components of Yiqi Zishen Formula(YZF)and their mechanisms for alleviating airway inflammation in mice with chronic obstructive pulmonary disease(COPD).Methods Ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry was employed to characterize the chemical components in YZF and YZF-medicated rat serum.A compound-disease target network was constructed based on serum components of YZF to screen the key pathways and targets using enrichment analysis.A mouse model of cigarette smoke-induced COPD was used to evaluate the anti-inflammatory effect of YZF and validate the expression of key proteins in network pharmacology-enriched pathways.Fifty male C57BL/6J mice were randomized equally into control group,COPD model group,high-and low-dose YZF treatment groups,and N-acetylcysteine treatment group.Pulmonary function of the mice was assessed using whole-body plethysmography,and lung histopathology,alveolar structure,and airway remodeling were analyzed using HE staining.The levels of IL-1β,IL-6,and TNF-α in bronchoalveolar lavage fluid(BALF)were determined with ELISA,and pulmonary expressions of PI3K,Akt,phosphorylated Akt(p-Akt),p65,and phosphorylated p65(p-p65)were detected using immunohistochemistry.Results We identified a total of 156 chemical components(including 26 flavonoids or flavonoid glycosides,27 alkaloids,and 11 saponins)in YZF and 43 prototype components in medicated rat serum.Network pharmacology revealed 704 YZF-related targets and 1199 COPD-associated targets.Integrated analysis suggested that the anti-COPD effects of YZF were associated with the PI3K-Akt signaling pathway.In mouse models of COPD,YZF treatment significantly increased mean alveolar number and peak expiratory flow(P<0.05),reduced mean linear intercept,bronchial wall thickness,lung coefficient,and BALF cytokine levels,and suppressed the expressions of PI3K,Akt,p-Akt,p65,and p-p65 in the lung tissues.Conclusion YZF alleviates COPD symptoms and airway inflammation in mice possibly by inhibiting the PI3K/Akt/NF-κB pathway through its multiple components that interact with multiple targets.关键词
益气滋肾方/慢性阻塞性肺疾病/入血成分/网络药理学/炎症Key words
Yiqi Zishen Formula/chronic obstructive pulmonary disease/serum-absorbed components/network pharmacology/inflammation引用本文复制引用
王立明,陈宏睿,杜燕,赵鹏,王玉洁,田燕歌,刘新光,李建生..益气滋肾方通过抑制PI3K/Akt/NF-κB通路改善小鼠慢性阻塞性肺疾病的炎症反应[J].南方医科大学学报,2025,45(7):1409-1422,14.基金项目
国家重点研发计划中医药现代化重点专项2023年度"揭榜挂帅"项目(2023YFC3502605) （2023YFC3502605）
国家自然科学基金(82274274) （82274274）
中华中医药学会青年人才托举工程(2023-QNRC2-B05) （2023-QNRC2-B05）
河南省高校创新人才支持项目(25HASTIT060) （25HASTIT060）
河南省科技研发计划联合基金(优势学科培育类)项目(222301420020)Supported by National Natural Science Foundation of China(82274274). （优势学科培育类）
