| Abstrakt: |
Objective To explore the role of 4-hydroxynonenal (HNE) in alleviating acute lung injury (ALI) induced by neonatal sepsis by inhibiting the focal death of endothelial cells (ECs). Methods Newborn mice were randomly divided into five groups: (1) Sham operation group (Sham group), (2) sham operation mice receiving HNE treatment group (Sham + HNE group), (3) cecal serosity (CS group), and (4) CS-treated GS-DMD-/- mice group (CS + GSDMD-/- group). The degree of lung injury was evaluated by lung histopathology and lung wet/dry weight ratio. The ECs of mice were isolated and divided into the Ctrl group, LPS + ATP group, LPS + ATP + HNE-L group and LPS + ATP + HNE-H group. Western blot was used to evaluate the expression of HNE and caspase-1 pathway. Results Compared with CS group, the lung tissue scores of CS + HNE group and CS + GSDMD-/- group were significantly decreased (P < 0.05), and the ratio of wet to dry weight of lung tissues was significantly decreased (P < 0.05). Compared with the CS group, the 72-hour survival rates of mice in the CS + HNE group and CS + GSDMD-/- group were significantly improved (P < 0.05). The expressions of GSDMD-N, C-caspase-1, NLRP3, IL-18 and IL-1β in lung ECs of the CS + HNE group and CS + GSDMD-/- group were significantly lower than those of the CS group (P < 005). Compared with the Ctrl cells, LPS + ATP significantly decreased the cell viability (P < 0.05) and increased the protein expressions of GSDMD, C-caspase-1, NLRP3, IL-18 and IL-1β (P < 0.05), and these effects were also inhibited by HNE. Conclusion HNE can inhibit the focal death of lung ECs cells by inhibiting NLRP3/caspase-1 signal transduction, and improve ALI in septic mice. [ABSTRACT FROM AUTHOR] |
