Influences of Morin hydrate on pyroptosis of alveolar epithelial cells in rats with chronic obstructive pulmonary disease by inhibiting NLRP3/Caspase-1/IL-1β signaling pathway
Objective:To investigate the mechanism of Morin hydrate(MH)on pyroptosis of alveolar epithelial cells in rats with chronic obstructive pulmonary disease(COPD)by inhibiting nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(Caspase-1)/IL-1β signaling pathway.Methods:COPD model rats were estab-lished by smoking method,which were randomly divided into model group(COPD group),low,medium and high doses MH groups(MH-L,MH-M,MH-H groups)(50,100,200 mg/kg)and positive control group(dexamethasone group,DXMS,0.09 mg/kg),another 10 healthy rats were taken as normal control group(NC group).Pulmonary function indexes[tidal volume(TV),forced vital capacity(FVC)and peak expiratory flow rate(PEF)]were measured;HE staining was used to observe pathological changes of lung tissue;pyroptosis of alveolar epithelial cells was observed by immunofluorescence double staining;levels of inflammatory factors in bronchoalveolar lavage fluid(BALF)were detected by ELISA;levels of NLRP3,Caspase-1,gasdermin D(GSDMD)and IL-1β mRNA were detected by RT-qPCR;protein expressions of SP-C,NLRP3,C-Caspase-1,GSDMD,GSDMD-N and IL-1β in lung tissue were detected by Western blot.Results:Compared with COPD group,pathological changes of lung tissue including lumen stenosis,mucus secretion and bronchial epithelial cell necrosis in DXMS group and MH groups were significantly improved,the pulmonary function indexes(TV,FVC,PEF)were increased obviously(P<0.05),and increased in turn in MH-L,MH-M,MH-H groups(P<0.05);levels of TNF-α,IL-6,IL-8,immunofluorescence expressions of NLRP3 and C-Caspase-1,and mRNA levels of NLRP3,Cas-pase-1,GSDMD,IL-1β,protein levels of NLRP3,C-Caspase-1,GSDMD,GSDMD-N and IL-1β were decreased obviously,while SP-C protein expression was gradually increased(P<0.05).Conclusion:MH can inhibit the NLRP3/Caspase-1/IL-1β signaling path-way,the release of inflammatory factors and pyroptosis by it,and alleviate lung pathological changes in COPD rats.
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