芒果苷抑制脂多糖诱导小鼠肺泡巨噬细胞炎症反应的机制研究OA北大核心CSTPCD

[Objective]The objective of this study was to analyze the inhibition mechanisms of mangiferin on lipopoly-saccharide(LPS)-induced inflammatory response,with the goal of identifying a potential therapeutic agent for sepsis.[Method]In this research,mouse alveolar macrophage(MH-S)were chosen as the subject of investigation,and the cyto-toxic impact of mangiferin on MH-S was assessed using the CCK-8 assay.According to the cytotoxicity test,the concen-tration of mangiferin was 100 μg/mL.With normal cultured MH-S as the control,10 μg/mL LPS was used for 24 h to con-struct an in vitro inflammatory model(LPS group),and then 100 μg/mL mangiferin was intervened for 24 h(intervention group).The contents of inflammatory factors(IL-1β,TNF-α,IL-6 and IL-18)in MH-S supernatants were measured by ELISA,gene expression of IL-1β,TNF-α,IL-6 and IL-18 was assessed using real-time fluorescence quantitative PCR,and changes in TLR4/NF-κB signaling pathway were measured by Western blotting and immunofluorescence.[Result]Mangiferin did not have obvious toxic effect on MH-S when its concentration was below 287.60 μg/mL.Compared with the control group,the relative expression of IL-1β,TNF-α,IL-6 and IL-18 was extremely significantly increased in the LPS group(P<0.01,the same below),and the contents of IL-1β,TNF-α,IL-6 and IL-18 in the cell supernatant was sig-nificantly(P<0.05,the same below)or extremely significantly increased.Following treatment with mangiferin interven-tion,there was significant decrease in both relative expression levels of IL-1β,TNF-α,IL-6 and IL-18 genes and their se-cretion levels,suggesting that mangiferin could alleviate inflammatory response in MH-S induced by LPS.In addition,relative expression of NF-κB gene and protein expression level in MH-S of LPS group were extremely significantly higher than that of the control group,and the relative expression of NF-κB gene and protein expression level decreased signifi-cantly after mangiferin intervention,indicating that mangiferin could effectively inhibit expression of nuclear transcrip-tion factors in MH-S induced by LPS;the TLR 4 expression level on the surface of MH-S of LPS group was greatly in-creased,but the TLR 4 expression level on MH-S surface decreased greatly after mangiferin intervention,indicating that mangiferin could effectively inhibit TLR 4 expression on the surface of MH-S induced by LPS.[Conclusion]Mangiferin has no obvious inhibitory effect on the proliferation of MH-S cells,and the half proliferation inhibition rate(IC50)of man-giferin is 287.60 μg/mL.Mangiferin has fine protective effect against the LPS-induced inflammatory response in MH-S,and the mechanism of action may be related to the reduction of inflammatory factor secretion by inhibiting the activation of TLR4/NF-κB signaling pathway.