小鼠内毒素性急性肺损伤时内质网IRE1α-XBP1信号通路与NETs的关系
Relationship between IRE1α/XBP1 signaling pathway in endoplasmic reticulum and neutrophil ex-tracellular traps during endotoxin-induced acute lung injury in mice
王宜博 1张琦 1孙莉莉 2周家骅 1徐瑞金 3孙立新 1马福国 1韩伟4
作者信息
- 1. 青岛市市立医院麻醉科,青岛 266071
- 2. 青岛市妇女儿童医院肾脏免疫科 266034
- 3. 青岛市市立医院干部保健一科 青岛 266071
- 4. 青岛市市立医院呼吸与危重症医学科,青岛 266071
- 折叠
摘要
目的 评价小鼠内毒素性急性肺损伤(ALI)时内质网肌醇需要酶1α-X盒结合蛋白1(IRE1α-XBP1)信号通路与中性粒细胞胞外诱捕网(NETs)的关系.方法 SPF级健康雄性C57BL/6小鼠48只,6～8周龄,体质量25～30 g,采用随机数字表法分为4组(n=12):对照组(C组)、STF-083010组(ST组)、内毒素性ALI组(ALI组)和内毒素性ALI+STF-083010组(ALI+ST组).ALI组和ALI+ST组采用雾化吸入LPS的方法建立小鼠内毒素性ALI模型,C组和ST组雾化吸入等量生理盐水,ST组和ALI+ST组于建模前1 h腹腔注射IRE1α抑制剂STF-083010 50 mg/kg,其余2组腹腔注射等容量生理盐水.建模后24 h时麻醉后处死小鼠,收集支气管肺泡灌洗液(BALF)与肺组织,光镜下观察肺组织病理学结果并行肺损伤评分,确定肺湿质量/干质量(W/D)比值;ELISA法测定BALF IL-1β、IL-18和髓过氧化物酶(MPO)浓度;Western blot法检测肺组织p-IRE1α、XBP1s和瓜氨酸化组蛋白3(CitH3)表达.结果 与C组相比,ALI组和ALI+ST组建模后24 h时肺损伤评分、W/D比值、BALF IL-1β、IL-18 和 MPO 浓度升高,肺组织 p-IRE1α、XBP1s 和 Cit H3 表达上调(P＜0.05);与 L组相比,ALI+ST组建模后24 h时肺损伤评分、W/D比值、BALF 1L-1β、IL-18和MPO浓度降低,肺组织p-IRE1α、XBP1s和Cit H3表达下调(P＜0.05).结论 IRE1α-XBP1信号通路参与了小鼠内毒素性ALI的过程,与上调NETs表达有关.
Abstract
Objective To evaluate the relationship between inositol-requiring enzyme 1α-X box-binding protein 1(IRE1α-XBP1)signaling pathway in endoplasmic reticulum and neutrophil extracellular traps during endotoxin-induced acute lung injury(ALI)in mice.Methods Forty-eight SPF healthy male C57BL/6 mice,aged 6-8 weeks,weighing 25-30 g,were divided into 4 groups(n=12 each)using a ran-dom number table method:control group(C group),STF-083010 group(ST group),lipopolysaccharide(LPS)-induced ALI group(ALI group)and LPS-induced ALI+STF-083010 group(ALI+ST group).The ALI model was established by inhaling aerosolized LPS in ALI group and ALI+ST group.The equal volume of aerosolized normal saline was inhaled in C and ST groups.IRE 1α inhibitor STF-083010 50 mg/kg was in-traperitoneally injected at 1 h before developing the model in ST and ALI+ST groups,and the equal volume of normal saline was intraperitoneally injected in the other two groups.The mice were sacrificed after anes-thesia at 24 h after developing the model.Bronchoalveolar lavage fluid(BALF)and lung tissues were col-lected for determination of the pathological changes(by light microscopy)which were scored,wet/dry lung weight(W/D)ratio,concentrations of interleukin-1beta(IL-1β),IL-18 and myeloperoxidase(MPO)in the BALF supernatant,and expression of phosphorylated IRE 1α(p-IRE1α),XBP1s and citrullinated his-tone H3(Cit H3)in lung tissues(using Western blot).Results Compared to group C,the lung injury scores and W/D ratio were significantly increased at 24 h after developing the model,the concentrations of IL-1β,IL-18 and MPO in BALF were increased,and the expression of p-IRE1α,XBP1s and Cit H3 in lung tissues was up-regulated in ALI and ALI+ST groups.Compared to group L,the lung injury scores and W/D ratio were significantly decreased at 24 h after developing the model,the concentrations of IL-1β,IL-18 and MPO in BALF were decreased,and the expression of p-IRE1α,XBP1s and Cit H3 in lung tis-sues was down-regulated in group ALT+ST(P＜0.05).Conclusions The IRE1α-XBP1 signaling pathway in endoplasmic reticulum is involved in endotoxin-induced ALI by up-regulating the expression of neutrophil extracellular traps in mice.
关键词
内毒素类/急性肺损伤/内质网/X盒结合蛋白1/胞外诱捕网Key words
Endotoxins/Acute lung injury/Endoplasmic reticulum/X-box binding protein 1/Extracellular traps引用本文复制引用
出版年
2024
NETL
NSTL
万方数据