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

WANG Huijuan; LEI Jiaxi; PAN Mingliang; ZOU Lijuan; LIU Shiping; ZHANG Yunlong; ZHU Xue; WAN Lu; ZHANG Zhaocai; SONG Zhenju; ZHAN Liying

doi:10.14188/j.1671-8852.2024.0513

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

更新时间：2026-11-05

- Hemoglobin subunit beta alleviates sepsis⁃induced acute lung injury by regulating the NRF2/HO⁃1 pathway
- Medical Journal of Wuhan University Vol. 46, Issue 2, Pages: 135-141(2025)
- 作者机构：
  
  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
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0513
  CLC： R34
- Received：09 July 2024，
  
  Published：25 February 2025
- 稿件说明：
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王慧娟,雷佳羲,潘明亮等.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[J].武汉大学学报（医学版）,2025,46(02):135-141.

WANG Huijuan,LEI Jiaxi,PAN Mingliang,et al.Hemoglobin subunit beta alleviates sepsis⁃induced acute lung injury by regulating the NRF2/HO⁃1 pathway[J].Medical Journal of Wuhan University,2025,46(02):135-141.
王慧娟,雷佳羲,潘明亮等.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[J].武汉大学学报（医学版）,2025,46(02):135-141. DOI： 10.14188/j.1671-8852.2024.0513.

WANG Huijuan,LEI Jiaxi,PAN Mingliang,et al.Hemoglobin subunit beta alleviates sepsis⁃induced acute lung injury by regulating the NRF2/HO⁃1 pathway[J].Medical Journal of Wuhan University,2025,46(02):135-141. DOI： 10.14188/j.1671-8852.2024.0513.

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。

Abstract

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

Keywords

references

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