Mechanism of Xuanfei Baidu Decoction to improve ALI mice by regulating TLR4/NLRP3/Caspase1 signaling pathway
[Objective]Pharmacodynamic effects and mechanism of Xuanfei Baidu Decoction(XFBD)on IgG-IC-induced acute lung injury(ALI)in mice based on the Toll-like receptor 4(TLR4)/NOD-like receptor family pyrin domain containing 3(NLRP3)/Cysteine aspartate protein hydrolase-1(Caspase 1)signaling pathway.[Methods]An ALI model was constructed using IgG-IC-induced mice,and XFBD 4 g raw/kg and 8 g raw/kg were administered by gavage in a single dose;pathological changes in lung tissue were observed by hematoxylin-eosin staining(HE).Cell viability was determined by lactate dehydrogenase(LDH)kit.And the fluorescence quantitative PCR was performed to detect the cytokines that include interleukin-6(IL-6),interleukin-18(IL-18),interleukin-1 β(IL-1 β)and monocyte chemotactic protein-1(MCP-1)in mouse lung tissue,and TLR4/NLRP3/Caspase1 signaling pathway related factors mRNA expression.Immunohistochemistry to detect the expression of TLR4,NLRP3,and Gasdermin-D(GSDMD)proteins in mouse lung tissues,and western blotting to detect the protein expression of Occludin,(Zonula occluding-1)ZO-1 and TLR4/NLRP3/Caspase1 signaling pathway related factors were detected by immunohistochemistry.[Results]Compared with the control group,mice in the model group had lung tissue inflammatory cell infiltration,alveolar interstitial thickening,significantly higher lung histopathological injury scores and lung tissue organ coefficients,exceedingly higher expression of LDH and cytokines,down-regulated expression of Occludin and ZO-1,and extraordinary higher mRNA and protein levels of factors related to the TLR4/NLRP3/Caspase1 signaling pathway.Compared with the model group,XFBD significantly alleviated inflammatory cell infiltration in lung tissues of mice with acute lung injury,reduced cytokine expression,up-regulated Occludin and ZO-1,and greatly down-regulated mRNA and protein levels of factors related to the TLR4/NLRP3/Caspase1 signaling pathway.[Conclusion]XFBD can exert anti-ALI effects in mice by modulating the TLR4/NLRP3/Caspase1 signaling pathway.
万方数据
维普
