E3泛素连接酶COP-1在脂多糖致小鼠急性肺损伤中的意义  

Significance of E3 ubiquitin ligase COP-1 in lipopolysaccharide-induced acute lung injury in mice

作　　者：方晓铵 熊欢庆 李玉娟 刘刚 金发光 Fang Xiaoan;Xiong Huanqing;Li Yujuan;Liu Gang;Jin Faguang(Department of Respiratory and Critical Care Medicine,The Second Affiliated Hospital of Air Force Medical University,Xi′an 710038,China)

机构地区：[1]空军军医大学第二附属医院呼吸与危重症医学科,西安710038

出　　处：《中华肺部疾病杂志（电子版）》2024年第1期14-18,共5页Chinese Journal of Lung Diseases(Electronic Edition)

基　　金：国家自然科学基金面上项目(81970076)。

摘　　要：目的 分析E3泛素连接酶组成型光形态发生蛋白1(constitutive photomorphogenetic protein 1, COP-1)全身敲除后的杂合子小鼠在脂多糖(lipopolysaccharide, LPS)致急性肺损伤(acute lung injury, ALI)中的表现及作用机制。方法 选择48只雄性C57小鼠,随机分为4组:已敲除COP-1:COP-1+/--PBS(KOPBS组)、COP-1+/--LPS(KOLPS组);未敲除COP-1:WT-PBS(WTPBS组)、WT-LPS(WTLPS组),每组12只。KOLPS组、WTLPS组给予LPS 10 mg/kg气管内滴注进行ALI造模,KOPBS组、WTPBS组用同等体积的PBS处理相同时间。造模24 h后,取肺组织,HE染色观察肺组织形态学改变,测定湿/干重比值(W/D),ELISA法测定肺泡灌洗液(bronchoalveolar lavage fluid, BALF)和肺组织中肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)、白介素-1β(interleukin-1β, IL-1β)、白介素-6(interleukin-6, IL-6)、肺组织中髓过氧化物酶(myeloperoxidase, MPO)活力。结果 形态学观察表明KOLPS组肺组织和WTLPS组、KOPBS组肺组织和WTPBS组比较炎性细胞浸润、充血、水肿显著。KOPBS组和WTPBS组,KOLPS组和WTLPS组比较,炎症因子水平以及肺组织中MPO活力和肺W/D比值升高(P<0.05)。结论 敲除小鼠E3泛素连接酶COP-1加重LPS致ALI,探讨COP-1在肺炎中治疗作用,具有临床意义。Objective To analyze the role of E3 ubiquitin ligase constitutive photomorphogenetic protein 1(COP-1)in lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice and preliminarily explore its mechanism of action.Methods All of 48 male C57 mice were randomly divided into 4 groups:COP-1 knockout:COP-1+/--PBS(KOPBS group),COP-1+/--LPS(KOLPL group);Non-knockout COP-1:WT-PBS(WTPBS group),WT-LPS(WTLPS group),12 in each group.Among them,the LPS group was given LPS 10 mg/kg intratracheally to model acute lung injury,while the PBS group was treated with an equal volume of PBS for the same time.24 hours after modeling,lung tissue was taken,HE stained to observe morphological changes in lung tissue,wet/dry weight ratio(W/D)was measured,ELISA was used to measure tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),myeloperoxidase(MPO)activity in lung tissue and bronchoalveolar lavage fluid(BALF).Results Morphological observations showed that infiltration of inflammatory cells,congestion,and edema in the KOLPS group lung tissue were more significant compared to the WT-LPS group,KOPBS group lung tissue,and the WTPBS group.Compared to the WTPBS group and KOPBS group,WTLPS group and KOLPS group,the level of inflammatory factors,MPO activity in lung tissue,and lung W/D ratio were significantly increased(P<0.05).Conclusion The knockout of E3 ubiquitin ligase COP-1 can aggravate LPS-induced acute lung injury in mice,the therapeutic effect of COP-1 in pneumonia needs further exploration.

关 键 词：急性肺损伤 E3泛素连接酶 组成型光形态发生蛋白1 炎症因子 

分 类 号：R563[医药卫生—呼吸系统]