Objective To explore the effect of leukotriene receptor antagonist montelukast on physicochemical property of sputum and airway mucus hypersecretion in patients with acute exacerbation of bronchiectasis. Methods Eighty-four inpatients with acute exacerbation of bronchiectasis were randomly divided into a control group and an experiment group, with 42 cases in each group. The control group received conventional therapy and the experiment group took orally montelukast 10 mg before sleep every day based on conventional therapy for two weeks. At admission and 15 days after admission, the amount in 24 hours, dry/wet weight ratio and viscosity of sputum were observed while the levels of neutrophil elastase (NE) and mucin MUC5ac in sputum were determined by ELISA. The pulmonary ventilation function, airway resistance and blood gas analysis were also measured. Results The sputum amount in 24 hours, dry/wet weight ratio and viscosity of sputum, NE and MUC5ac of sputum, pulmonary ventilation function, blood gas analysis and airway resistance were declined or improved remarkably after treatment compared with before treatment in two groups (P<0.05). Meanwhile, the sputum amount in 24 hours [(5.62±1.83) g vs. (7.53±2.32) g], NE [(3.85±0.97) μg/ml vs. (4.54±1.03) μg/ml], MUC5ac [(0.65±0.21) μg/ml vs. (0.82± 0.29) μg/ml] and the airway resistance [(119.16±11.76)% vs. (128.37±12.08)%] were declined remarkably in the experiment group compare with the control group after treatment (all P<0.05). The viscosity of sputum between the two groups after treatment showed no significant difference. Conclusion In patients with acute exacerbation of bronchiectasis, montelukast can reduce amount of sputum and airway resistance, reduce expression of mucin MUC5ac through down-regulation of NE, thus inhibit airway mucus hypersecretion.
Objective To investigate the effects of wedelolactone (WEL) on lipopolysaccharide (LPS)-induced pyroptosis of alveolar epithelial cells and AMP-activated protein kinase/nucleotide binding oligomeric domain like receptor 3 (NLRP3)/cysteinyl aspartate specific proteinase-1 (Caspase-1) signaling pathway. Methods Human lung epithelial cells BEAS-2B were treated with 5 - 200 μmol/L wedelolactone, and cell activity was detected using MTT assay. The alveolar epithelial cells were divided into control group, lipopolysaccharide group (LPS group), 10 μmol/L wedelolactone group (WEL-L group), 20 μmol/L wedelolactone group (WEL-M group), 40 μmol/L wedelolactone group (WEL-H group), 40 μmol/L wedelolactone+10 μmol/L AMPK inhibitor Compound C group (WEL-H+Compound C group), and 20 μmol/L Caspase-1 inhibitor Z-YVAD-FMK group (Z-YVAD-FMK group). Transmission electron microscopy was applied to observe the microstructure of cells. ELISA was applied to detect levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-8 (IL-8). Immunofluorescence was applied to detect Caspase-1 and gasdermin family proteins (DGSDMD). Western blot was applied to detect protein expression levels of AMPK, NLRP3, and Caspase-1. Results Wedelolactone concentrations of 10, 20 and 40 μmol/L were selected for follow-up experiments. Compared with Control group, LPS group showed decreased cell activity, severe damage, cell contraction, mitochondrial ridge breakage and decreased number, increased levels of TNF-α, IL-1β, IL-8 and GSDMD, NLRP3, Caspase-1 expression, and decreased p-AMPK/AMPK expression (P<0.05). Wedelolactone treatment could significantly improve LPS-induced pyrosis of alveolar epithelial cells (P<0.05). Compound C could partially reverse the effect of wedelactone on LPS-induced pyrodeath of alveolar epithelial cells (P<0.05). Z-YVAD-FMK treatment also significantly improved LPS-induced pyroptosis of alveolar epithelial cells (P<0.05). Conclusion Wedelolactone can inhibit LPS-induced pyroptosis of pulmonary alveolar epithelial cells by inhibiting AMPK/NLRP3/Caspase-1 signaling pathway.