Tongsai Granules inhibit autophagy and macrophage-mediated inflammatory response to improve acute exacerbations of chronic obstructive pulmonary disease in rats
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…
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