Abstract: Objective To investigate the mechanism of tea polyphenols (TP) for regulating NLRP3 inflammasomes and alleviating acute lung injury in septic mice. Methods Sixty C57BL/6 mice were randomly assigned into sham-operated, cecal ligation and puncture (CLP) and CLP + TP treatment groups, and survival of the mice was recorded after modeling in each group. The lung wet/dry weight ratio and myeloperoxidase (MPO) activity were determined, and lung injury of the mice was evaluated using HE staining and acute lung injury score. The expressions of IL-1β, TNF-α, IL-6, NLRP3, caspase-1 p10, ASC, MPO, and caspase-8 in the lung tissue were detected using ELISA, Western blotting, or immunohistochemical staining. MDA and H2O2 levels in the lungs were detected to evaluate the level of oxidative stress. Immunofluorescence assay was used to investigate the co-localization of NLRP3 and NOX4. Results The postoperative mortality rate at 72 h, lung wet/dry weight ratio, MPO level and acute lung injury scores were significantly lower in CLP+TP group than in CLP group (P<0.05). Treatment with TP significantly reduced the expressions of NLRP3- related inflammatory factors (P<0.05) and lowered MDA and H2O2 levels in the lung tissue of the septic mice (P<0.05). Immunofluorescence co-staining showed a lower level of NOX4 and NLRP3 co-localization in CLP+TP group than in CLP group. Conclusion TP inhibits NLRP3 inflammasome-associated inflammation to alleviate CLP-induced acute lung injury in mice through a regulatory mechanism that inhibits NOX4 expression and reduces oxidative stress in the lung tissue.

Key words: tea polyphenols; sepsis; acute lung injury; NLRP3 inflammasomes; oxidative stress