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  

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

作　　者：武周游 李婷[1] 张腾伟 房巧燕 杨刘 黎巧 WU Zhouyou;LI Ting;ZHANG Tengwei;FANG Qiaoyan;YANG Liu;LI Qiao(Department of Neonatology,Hunan Provincial Maternal and Child Health Hospital,Changsha 410008,China)

机构地区：[1]湖南省妇幼保健院新生儿一科,长沙410008

出　　处：《实用医学杂志》2024年第2期195-201,共7页The Journal of Practical Medicine

基　　金：湖南省卫生健康委员会科研计划项目(编号:202202891340);湖南省卫生健康委科研计划项目(编号:D202306036070)。

摘　　要：目的探讨4-羟基壬烯醛(HNE)通过抑制内皮细胞(ECs)焦亡在减轻新生儿脓毒症诱导的急性肺损伤(ALI)中的作用。方法新生小鼠随机分为5组:(1)假手术组(Sham组);(2)假手术小鼠接受HNE治疗组(Sham+HNE组);(3)盲肠浆液(cecal slurry,CS)处理组(CS组);(4)CS处理的GSDMD^(-/-)小鼠组(CS+GSDMD^(-/-)组);(5)CS小鼠接受HNE治疗组(CS+HNE组)。通过肺组织病理学和肺湿/干重量比评估肺损伤程度。分离小鼠ECs,并分为Ctrl组、LPS+ATP组、LPS+ATP+HNE-L组和LPS+ATP+HNE-H组。蛋白质印迹法评估HNE和Caspase-1途径表达。结果与CS组相比,CS+HNE组和CS+GSDMD^(-/-)组小鼠的肺组织评分显著降低(P<0.05),并且肺组织的湿和干重量比显著降低(P<0.05)。小鼠72 h存活率观察结果显示,与CS组相比,CS+HNE组和CS+GSDMD^(-/-)组小鼠的存活率显著提高(P<0.05)。CS+HNE组和CS+GSDMD^(-/-)组小鼠的肺ECs中GSDMD-N、C-caspase-1、NLRP3、IL-18、IL-1β表达显著低于CS组(P<0.05)。与Ctrl组细胞相比,LPS+ATP显著降低细胞活力(P<0.05),和增加了GSDMD、C-caspase-1、NLRP3、IL-18、IL-1β的蛋白表达(P<0.05),而这些作用也被HNE抑制。结论HNE可以通过抑制NLRP3/Caspase-1信号传导来抑制肺ECs细胞焦亡,并改善脓毒症小鼠的ALI。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-1βin lung ECs of the CS+HNE group and CS+GSDMD^(-/-)group were signifi⁃cantly 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.

关 键 词：4-羟基壬烯醛 内皮细胞 细胞焦亡 新生儿脓毒症 急性肺损伤 

分 类 号：R563[医药卫生—呼吸系统]