Tongsai Granules inhibit autophagy and macrophage-mediated inflammatory response to improve acute exacerbations of chronic obstructive pulmonary disease in rats
10.12122/j.issn.1673-4254.2024.10.18
- VernacularTitle:通塞颗粒阻抑巨噬细胞炎症反应改善大鼠慢性阻塞性肺疾病急性加重
- Author:
Mengmeng CHENG
1
,
2
,
3
;
Xinguang LIU
;
Yanxin WEI
;
Xiaoxiang XING
;
Lan LIU
;
Nan XIN
;
Peng ZHAO
Author Information
1. 河南中医药大学 呼吸疾病中医药防治省部共建协同创新中心//河南省中医药防治呼吸病重点实验室,河南 郑州 450046
2. 河南中医药大学 中医药科学院,河南 郑州 450046
3. 河南中医药大学第一附属医院呼吸科,河南 郑州 450046
- Keywords:
Tongsai Granule;
acute exacerbation of chronic obstructive pulmonary disease;
macrophages;
inflammatory response
- From:
Journal of Southern Medical University
2024;44(10):1995-2003
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the inhibitory effect of Tongsai Granules(TSG)on macrophage-mediated inflammatory response to alleviate acute exacerbation of chronic obstructive pulmonary disease(AECOPD)in rats and explore the underlying mechanism.Methods Twenty-four rats were divided into control group,AECOPD model group,TSG treatment group,and moxifloxacin+salbutamol(MXF+STL)treatment group.In the rat models of COPD,AECOPD was induced by nasal instillation of Klebsiella pneumoniae on day 3 of week 9 after modeling,and saline,TSG or MXF+STL were administered via gavage on days 1 and 2 and days 4 to 7 of week 9.After the treatments,lung tissues were collected for examining for pathologies and expressions of inflammatory markers,MMP2,and MMP9.In cultured macrophage MH-S cells with LPS stimulation,the effect of TSG-medicated serum on IL-1β,IL-6,TNF-α,COX-2,and iNOS expressions and phosphorylation levels of p38,p-p62,LC3,FoxO3a,and mTOR were evaluated.Results TSG significantly improved lung pathologies and lung function in AECOPD rats by reducing bronchial wall thickness and mean alveolar linear intercept,increasing alveolar numbers,and reducing pulmonary expression of IL-1β,IL-6,TNF-α,MMP2 and MMP9.In MH-S cells,TSG significantly suppressed LPS-induced expressions of inflammatory cytokines,COX-2 and iNOS.Serum pharmacology coupled with network pharmacology identified 10 chemical components in TSG-medicated serum,and functional analysis of their 466 targets suggested that the therapeutic effect of TSG on AECOPD was mediated primarily by luteolin and quercetin,which regulate the MAPK,mTOR,FoxO,and autophagy pathways.In MH-S cells,luteolin significantly inhibited LPS-induced inflammatory responses and expressions of p-p38,FoxO3a,mTOR,p-p62 and LC3.Conclusion TSG reduces macrophage-mediated inflammatory responses to alleviate AECOPD in rats possibly by modulating p38,mTOR,and FoxO3a pathways and inhibiting autophagy.
