铁死亡参与小鼠脓毒血症相关急性肺损伤的形成

Ferroptosis involved in sepsis-associated acute lung injury in mice

目的探究铁死亡是否参与小鼠脓毒血症相关急性肺损伤的形成。方法用盲肠结扎穿孔法,建立小鼠脓毒血症相关急性肺损伤模型。实验分为3组:假手术组、对穿一孔组和对穿二孔组。每组分别在术后1、2、3、5、7 d对小鼠进行肺组织取材,检测各组及各时间点的肺组织湿干重比(W/D)、还原型谷胱甘肽(GSH)、谷胱甘肽过氧化酶4(GPX4)和丙二醛(MDA)活性及组织铁含量。结果相较于假手术组,对穿一孔组和对穿二孔组W/D升高;GSH和GPX4活性下降;肺组织MDA活性增加,铁含量增加,以上指标呈时间和穿刺孔数依赖性改变。结论铁死亡参与了小鼠脓毒血症相关急性肺损伤的形成。

Objective To explore whether ferroptosis is involved in the sepsis-associated acute lung injury in mice.Methods A model of sepsis-associated acute lung injury in mice was established by cecal ligation and puncture.All the mice were randomly divided into three groups:sham operation group,one-hole ligation and puncture group,and two-hole ligation and puncture group.A sampling of lung tissues was conducted for each group at one day,two days,three days,five days,and seven days after the operation,respectively.The wet-to-dry weight(W/D)ratio,the activity of reduced glutathione(GSH),glutathione peroxidase 4(GPX4),and malondialdehyde(MDA)of lung tissue,and the iron content in the tissue at each time point were determined for each group.Results Compared with the sham operation group,both the one-hole ligation and puncture group and the two-hole ligation and puncture group showed an increase in the W/D ratio,the activity of MDA in the lung tissues,and iron content,with a decline in the activity of GSH and GPX4.The above indexes changed depending on the time and number of puncture holes.Conclusion Ferroptosis is involved in the sepsis-associated acute lung injury in mice.