Mechanism of Yupingfeng powder inhibiting airway inflammation in asthma through ZBP1-mediated alveolar macrophage PANoptosis
Objective:To observe the effect of Yupingfeng powder on ZBP1-mediated PANoptosis of alveolar macrophages so as to elucidate its molecular mechanism of inhibiting airway inflammation in asthma.Methods:Lipopolysaccharide was used to in-duce alveolar macrophages(MH-S)to construct an asthma cell model,and different concentrations of Yupingfeng powder medi-cated serum were given for intervention.CCK8 method was used to detect the activity of NH-S cells,ELISA method was used to detect the content of LDH,IL-1β and IL-18,flow cytometry was used to detect cell death,Western blot method was used to de-tect the expression of PANoptosis-related proteins and ZBP1 protein,and RT-qPCR method was used to detect the expression of ZBP1 gene.Results:Compared with the control group,the LDH release of alveolar macrophages,the content of IL-1β and IL-18 and the proportion of dead cells in the model group were significantly increased.The expressions of pyroptosis proteins(Cleaved caspase-1 and GSDMD-NT),necroptosis proteins(p-RIPK3 and p-MLKL),and apoptosis protein(Cleaved caspase-3)were significantly up-regulated(P<0.01).Compared with the model group,the expression of LDH release,the content of IL-1β and IL-18,and the proportion of dead cells in alveolar macrophages in the Yupingfeng powder group were significantly reduced,and the expression of Cleaved caspase-1,GSDMD-NT,p-RIPK3,p-MLKL,and Cleaved caspase-3 were significantly down-regulated(P<0.01).In addition,the expression of ZBP1 protein and ZBP1 mRNA in alveolar macrophages in the Yuping-feng powder group was significantly reduced compared with the model group,and the differences were statistically significant(P<0.01).Conclusion:Yupingfeng powder ameliorates airway inflammation by inhibiting the expression of ZBP1 in alveolar macro-phages,thereby suppressing the level of PANoptosis.
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