β⁃珠蛋白通过调控NRF2/HO⁃1通路减轻脓毒症诱导的急性肺损伤  

Hemoglobin subunit beta alleviates sepsis⁃induced acute lung injury by regulating the NRF2/HO⁃1 pathway

作　　者：王慧娟 雷佳羲 潘明亮 邹丽绢 刘世平 张云龙 竹雪 王璐[1] 张召才[3] 宋振举 詹丽英[1] WANG Huijuan;LEI Jiaxi;PAN Mingliang;ZOU Lijuan;LIU Shiping;ZHANG Yunlong;ZHU Xue;WAN Lu;ZHANG Zhaocai;SONG Zhenju;ZHAN Liying(Dept.of Critical Care Medicine,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China;Dept.of Surgical Intensive Care Unit,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,Shaanxi,China;Dept.of Critical Care Medicine,The Second Affiliated Hospital,Zhejiang University School of Medicine&Zhejiang Province Clinical Research Center for Emergency and Critical Care Medicine,Hangzhou 310009,Zhejiang,China;Dept.of Emergency,Zhongshan Hospital Fudan University&Institute of Emergency Rescue and Critical Care,Fudan University,Shanghai 200032,China)

机构地区：[1]武汉大学人民医院重症医学科,湖北武汉430060 [2]西安交通大学第一附属医院外科ICU,陕西西安710061 [3]浙江大学医学院附属第二医院重症医学科/浙江省急危重症临床医学研究中心,浙江杭州310009 [4]复旦大学附属中山医院急诊科/复旦大学应急救援与急危重症研究所,上海200032

出　　处：《武汉大学学报(医学版)》2025年第2期135-141,共7页Medical Journal of Wuhan University

基　　金：国家重点研发计划(编号:2021YFC2501800);国家自然科学基金面上项目(编号:82272226);武汉市知识创新专项项目(编号:2023020201010165);武汉大学人民医院交叉创新人才项目(编号:JCRCZN⁃2022⁃017)。

摘　　要：目的:探讨β⁃珠蛋白(HBB)在脓毒症急性肺损伤中的作用及机制。方法:雄性C57BL/6小鼠随机分成sham组、CLP组和AAV⁃HBB⁃CLP组。气管滴注腺病毒构建小鼠肺HBB过表达模型,肠结扎穿孔(CLP)法制备脓毒症肺损伤小鼠模型,HE染色观察肺组织病理形态,计算肺W/D;ELISA法检测小鼠血清中炎症因子TNF⁃α、IL⁃1β、IL⁃6和MCP⁃1水平;q⁃PCR与Western Blot法检测肺NRF2和HO⁃1的表达水平,免疫荧光法检测NRF2蛋白表达。人脐静脉内皮细胞(HUVECs)细胞分PBS组、LPS组和LPS⁃Lenti⁃HBB组,LPS处理后检测细胞中ROS含量。结果:相较于sham组,CLP组小鼠死亡率升高,肺损伤程度加重,血清TNF⁃α、IL⁃6、IL⁃1β、MCP⁃1和肺NRF2、HO⁃1表达增多;AAV⁃HBB⁃CLP组小鼠相较于CLP组死亡率降低,肺损伤程度下降,NRF2和HO⁃1表达升高,血清TNF⁃α、IL⁃6、IL⁃1β和MCP⁃1降低;细胞实验中,HBB显著降低LPS诱导的ROS含量。结论:HBB通过激活NRF2/HO⁃1减轻脓毒症小鼠的急性肺损伤。Objective:To investigate the mechanism of hemoglobin subunit beta(HBB)in acute lung injury caused by sepsis.Methods:Male C57BL/6 mice were randomly divided into three groups:the sham group,the cecal ligation and puncture(CLP)group,and the AAV⁃HBB⁃CLP group.The mouse lung HBB overexpression model was constructed by endotracheal injection of adenovirus,while the mouse lung injury model was prepared using the CLP method.The pathological morphology of the lung tissue was observed by HE staining,and the lung wet⁃to⁃dry(W/D)weight ratio was calculated.Serum levels of inflammatory cytokines TNF⁃α,IL⁃1β,IL⁃6,and MCP⁃1 were detected by ELISA.The expression levels of NRF2 and HO⁃1 in the lung were detected by qPCR and Western Blot,with NRF2 protein expression was detected by immunofluorescence.The cells were divided into three groups:the PBS group,the LPS group,and the LPS⁃Lenti⁃HBB group.ROS content in HUVECs was detected following LPS treatment.Results:Compared with the sham group,the CLP group showed increased mortality,lung injury,and serum levels of TNF⁃α,IL⁃6,IL⁃1β,MCP⁃1,as well as increased lung expression of NRF2 and HO⁃1.Compared with the CLP group,the AAV⁃HBB⁃CLP group exhibited decreased mortality,reduced lung injury,increased expression of NRF2 and HO⁃1,and decreased serum levels of TNF⁃α,IL⁃6,IL⁃1β,and MCP⁃1.In cell experiments,HBB significantly reduced LPS⁃induced ROS content.Conclusion:HBB alleviates sepsis⁃induced acute lung injury by activating NRF2/HO⁃1.

关 键 词：脓毒症 急性肺损伤 β⁃珠蛋白 NRF2 HO⁃1 氧化应激 

分 类 号：R34[医药卫生—基础医学]