The Journal of Practical Medicine >
Hydroxynonenal alleviates neonatal sepsis⁃induced acute lung injury by inhibiting endothelial cell pyrosis
Received date: 2023-05-28
Online published: 2024-03-06
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 GSDMD-/- 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.
Key words: 4-hydroxynonenal; endothelial cells; cell scorch; neonatal sepsis; acute lung injury
Zhouyou WU , Ting LI , Tengwei ZHANG , Qiaoyan FANG , Liu YANG , Qiao LI . Hydroxynonenal alleviates neonatal sepsis⁃induced acute lung injury by inhibiting endothelial cell pyrosis[J]. The Journal of Practical Medicine, 2024 , 40(2) : 195 -201 . DOI: 10.3969/j.issn.1006-5725.2024.02.012
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