Nobiletin alleviates sepsis‑induced acute lung injury by regulating endoplasmic reticulum stress

LIU Shiping; ZHANG Yunlong; ZOU Lijuan; WANG Huijuan; PAN Mingliang; ZHU Xue; ZHANG Zhaocai; ZHAN Liying

doi:10.14188/j.1671-8852.2024.0518

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Nobiletin alleviates sepsis‑induced acute lung injury by regulating endoplasmic reticulum stress

更新时间：2026-11-05

- Nobiletin alleviates sepsis‑induced acute lung injury by regulating endoplasmic reticulum stress
- Medical Journal of Wuhan University Vol. 46, Issue 2, Pages: 160-165(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.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
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0518
  CLC： R34
- Received：10 July 2024，
  
  Published：25 February 2025
- 稿件说明：
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刘世平,张云龙,邹丽绢等.川陈皮素通过调控内质网应激减轻脓毒症急性肺损伤[J].武汉大学学报（医学版）,2025,46(02):160-165.

LIU Shiping,ZHANG Yunlong,ZOU Lijuan,et al.Nobiletin alleviates sepsis‑induced acute lung injury by regulating endoplasmic reticulum stress[J].Medical Journal of Wuhan University,2025,46(02):160-165.
刘世平,张云龙,邹丽绢等.川陈皮素通过调控内质网应激减轻脓毒症急性肺损伤[J].武汉大学学报（医学版）,2025,46(02):160-165. DOI： 10.14188/j.1671-8852.2024.0518.

LIU Shiping,ZHANG Yunlong,ZOU Lijuan,et al.Nobiletin alleviates sepsis‑induced acute lung injury by regulating endoplasmic reticulum stress[J].Medical Journal of Wuhan University,2025,46(02):160-165. DOI： 10.14188/j.1671-8852.2024.0518.

摘要

目的

探讨川陈皮素减轻脓毒症急性肺损伤的作用机制。

方法

雄性C57BL/6 小鼠随机分为Sham组、CLP组和CLP+NOB（川陈皮素）组。所有小鼠术后24 h取肺组织，HE染色观察肺组织病理形态及Smith评分；计算肺组织湿重干重比（W/D）；蛋白质免疫印迹法检测肺组织中内质网应激蛋白IRE1的表达水平。小鼠肺泡巨噬细胞（MHS）分为PBS组、LPS组和LPS+NOB组。流式细胞术检测巨噬细胞M1极化；使用DCFH‑DA荧光探针检测细胞中活性氧（ROS）水平；酶联免疫吸附试验（ELISA）检测细胞上清液中炎症因子IL‑6和TNF‑α的含量。

结果

与Sham组小鼠比较，CLP组小鼠肺组织损伤程度加重，Smith评分及W/D显著升高，肺组织中内质网应激蛋白IRE1的表达水平显著升高（

0.05）；与CLP组比较，CLP+NOB组小鼠肺组织损伤程度减轻，Smith评分及W/D显著下降，肺组织内质网应激蛋白IRE1表达水平显著降低（

0.05）。细胞实验结果显示：与PBS比较，LPS组MHS细胞向M1极化增加，炎症因子和ROS产生显著增多（

0.05）；而与LPS组比较，LPS+NOB组MHS细胞向M1极化显著减少，炎症因子和ROS水平降低（

0.05）。

结论

川陈皮素可能通过调控内质网应激减轻小鼠脓毒症急性肺损伤。

Abstract

Objective

To investigate the mechanism of Nobiletin in alleviating sepsis‑induced acute lung injury.

Methods

Male C57BL/6 mice were randomly divided into three groups: the Sham group

the CLP group

and the CLP+NOB (Nobiletin) group. Lung samples were collected 24 hours after modeling

and the pathological morphology of the lung tissue was observed and scored using HE staining. Additionally

the wet⁃to⁃dry weight ratio was calculated. Western Blot was used to detect the levels of the endoplasmic reticulum stress protein IRE1 in lung tissue. Mouse alveolar macrophages (MHS) were divided into three groups: the PBS group

the LPS group

and the LPS+NOB group. Flow cytometry was used to detect the level of M1⁃like macrophages

the level of reactive oxygen species (ROS) was detected using the DCFH⁃DA fluorescence probe

and the levels of inflammatory factors IL⁃6 and TNF⁃α in the cell supernatant were assessed by ELISA.

Results

Compared with the Sham group

the CLP group exhibited severe lung tissue injury

significant increases in Smith score and lung wet‑to‑dry weight ratio

and remarkably elevated protein levels of the endoplasmic reticulum stress protein IRE1 in lung tissue (

0.05). Compared with the CLP group

the CLP+NOB group showed remarkable alleviation of lung tissue injury

notable reductions in Smith score and lung wet‑to‑dry weight ratio

and decreased levels of endoplasmic reticulum stress protein IRE1 in lung tissue (

0.05). Results of the cell experiment showed that

compared with the PBS group

the LPS group exhibited increased levels of M1⁃like macrophages

elevated levels of ROS

and increased levels of inflammatory factors (

0.05). Compared with the LPS group

the LPS+NOB group exhibited inhibition polarization of MHS macrophages to M1

and reduced levels of ROS and inflammatory factors (

0.05).

Conclusion

Nobiletin can alleviate sepsis⁃induced acute lung injury in mice

potentially through its mechanism of regulating endoplasmic reticulum stress.

关键词

Keywords

references

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