Abstract: Objective This study was to investigate the effects of FOXO4 on lipopolysaccharide(LPS) -induced inflammation and apoptosis of cardiomyocytes, and to explore the potential molecular mechanism. Methods LPS treated H9C2 cells were treated with FOXO4 recombinant lentiviralvector (LPS + Lv-FOXO4), control vector ( LPS + Lv-NC group) and / or nigericin ( LPS + LvFOXO4 + N group) respectively. Real-time quantitative polymerase chain reaction ( RT-qPCR) was used to detect the expression level of FOXO4 mRNA. The levels of TNF-α and IL-1β in cell supernatant were detected by enzyme-linked immunosorbent assay. The apoptosis was detected by flow cytometry. The expression levels of FOXO4 and NF-κB / NLRP3 pathway-related proteins was analyzed by Western blotting. Results LPS treatment could inhibit the expression of FOXO4 in myocytes (P < 0. 05), while overexpression of FOXO4 could decrease the levels of TNF-α and IL-1β,inhibit the apoptosis of myocytes, decrease the expression level of pro-apoptotic protein Bax and increase the expression level of anti-apoptotic protein Bcl-2 in myocytes treated with LPS (P < 0. 05).In addition, overexpression of FOXO4 could inhibit the activation of NF-κB signaling pathway by inhibiting P65, IκBα phosphorylation and P65 nuclear shift ( P < 0. 05). Overexpression of FOXO4inhibited NLRP3 inflammasome activation and pyroptosis by inhibiting NLRP3, ASC, cleavedcaspase-1, and N-GSDMD protein expression ( P < 0. 05 ). The NLRP3 inflammasome activator Nigeritin could reverse the protective effect of FOXO4 overexpression on LPS-induced myocardialcell injury ( P < 0. 05). Conclusion Overexpression of FOXO4 can protect cardiomyocytes fromLPS-induced inflammation and apoptosis, possibly by inhibiting pyroptosis mediated by NF-κB / NLRP3 inflammasome signaling pathway.

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