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 extracellular traps during endotoxin-induced acute lung injury in mice

作　　者：王宜博 张琦 孙莉莉 周家骅 徐瑞金[3] 孙立新[1] 马福国[1] 韩伟[4] Wang Yibo;Zhang Qi;Sun Lili;Zhou Jiahua;Xun Ruijin;Sun Lixin;Ma Fuguo;Han Wei(Department of Anesthesiology,Qingdao Municipal Hospital,Qingdao 266071,China;Department of Nephrology and Immunology,Qingdao Women and Children′s Hospital,Qingdao 266034,China;Department of the Cadre Health Care,Qingdao Municipal Hospital,Qingdao 266071,China;Department of Respiratory and Critical Care Medicine,Qingdao Municipal Hospital,Qingdao 266071,China)

机构地区：[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

出　　处：《中华麻醉学杂志》2024年第7期871-875,共5页Chinese Journal of Anesthesiology

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-08301050 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(Cit H3)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 IL-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。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 random 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.IRE1αinhibitor STF-08301050 mg/kg was intraperitoneally 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 anesthesia at 24 h after developing the model.Bronchoalveolar lavage fluid(BALF)and lung tissues were collected 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 IRE1α(p-IRE1α),XBP1s and citrullinated histone 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 tissues was down-regulated in group ALT+ST(P<0.05).Conclusions The IRE1α-XBP1 signal

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 

分 类 号：R563.8[医药卫生—呼吸系统]