摘要
OBJECTIVE:To explore the underlying mechanisms of the effects of Yangqing Chenfei formula(养清尘肺方,YCF) on inflammation and fibrosis in silicosis via inhibition of macrophage polarization.METHODS:A silicotic rat model was established via a single intratracheal instillation of silica particles on the first day of week 0.Subsequently,YCF was administered intragastrically to silicotic rats during weeks 0-2 and 5-8 twice daily.The mouse-derived alveolar macrophage cell line was used to investigate the mechanisms of YCF in M1/M2 polarization.RESULTS:YCF treatment effectively inhibited lung pathological changes,including inflammatory cell infiltration and tissue damage,and increased the forced expiratory volume in the first 0.3 s,functional residual capacity,and maximal mid-expiratory flow in weeks 2 and 8.Furthermore,the treatment improved lung functions by upregulating tidal volume,pause increase,and expiratory flow at 50% tidal volume from weeks 5 to 8.Moreover,YCF could significantly suppressed the progression of inflammation and fibrosis,by reducing the levels of inflammatory cytokines,as well as collagen-Ⅰ and Ⅲ.YCF treatment also decreased the numbers of macrophages and M1/M2 macrophages and the level of transforming growth factor-β(TGF-β).Additionally,YCF5,the effective substance in YCF,decreased lipopolysaccharide and interferon-γ-induced M1 macrophage polarization in a concentration-dependent manner.The mechanism of anti-M1 polarization might be related to a decrease in extracellular signal-regulated kinase,c-JUN N-terminal kinase,P38,and P65 phosphorylation.Furthermore,YCF5 inhibited interleukin-4-induced M2 macrophages by decreasing the protein and m RNA expressions of arginase-1 and CD206 as well as the levels of profibrotic factors,such as TGF-β and connective tissue growth factor.The mechanisms underlying the anti-M2 polarization of YCF5 were primarily associated with the inhibition of the nuclear translocation of phosphorylated signal transducer and activator of transcription 6(pSTAT6).CONCLUSION:YCF significantly inhibits inflammation and fibrosis in silicotic rats probably via the suppression of M1/M2 macrophage polarization mediated by the inhibition of mitogen-activated protein kinase and nuclear factor kappa B signaling pathways and Janus kinase/STAT6 pathways.
基金
Special Project of Traditional Chinese Medicine Research of Henan Province(2021ZYZD01)
Evaluation of the Therapeutic Effect and Characteristics of Traditional Chinese Medicine Dialectical Treatment for Coal Worker's Pneumoconiosis Based on A Multicenter,Randomized,Double-Blind,Parallel Controlled Trial
National Natural Science Fund of China(81973822)
Exploring the Mechanism of Bufei Yishen Formula Inhibiting Inflammatory Response in the Treatment of COPD Based on Group Allocation Theory。