羟基壬烯醛通过抑制内皮细胞焦亡减轻新生儿脓毒症诱导的急性肺损伤

doi:10.3969/j.issn.1006-5725.2024.02.012

Abstract

Abstract:

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

CLC Number:

R563

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.

Figures/Tables 5

References 22

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Hydroxynonenal alleviates neonatal sepsis⁃induced acute lung injury by inhibiting endothelial cell pyrosis

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