Esketamine alleviates septic lung injury via Keap1/Nrf2⁃HO⁃1 pathway

ZHANG Xinyu; ZHANG Jiancheng; YUAN Shiying

doi:10.14188/j.1671-8852.2024.0495

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Esketamine alleviates septic lung injury via Keap1/Nrf2⁃HO⁃1 pathway

更新时间：2026-11-05

- Esketamine alleviates septic lung injury via Keap1/Nrf2⁃HO⁃1 pathway
- Medical Journal of Wuhan University Vol. 46, Issue 2, Pages: 147-152(2025)
- 作者机构：
  
  华中科技大学同济医学院附属协和医院重症医学科湖北武汉 430022
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0495
  CLC： R563.8
- Received：04 July 2024，
  
  Published：25 February 2025
- 稿件说明：
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张鑫宇,张建成,袁世荧.艾司氯胺酮通过Keap1/Nrf2⁃HO⁃1减轻脓毒症肺损伤[J].武汉大学学报（医学版）,2025,46(02):147-152.

ZHANG Xinyu,ZHANG Jiancheng,YUAN Shiying.Esketamine alleviates septic lung injury via Keap1/Nrf2⁃HO⁃1 pathway[J].Medical Journal of Wuhan University,2025,46(02):147-152.
张鑫宇,张建成,袁世荧.艾司氯胺酮通过Keap1/Nrf2⁃HO⁃1减轻脓毒症肺损伤[J].武汉大学学报（医学版）,2025,46(02):147-152. DOI： 10.14188/j.1671-8852.2024.0495.

ZHANG Xinyu,ZHANG Jiancheng,YUAN Shiying.Esketamine alleviates septic lung injury via Keap1/Nrf2⁃HO⁃1 pathway[J].Medical Journal of Wuhan University,2025,46(02):147-152. DOI： 10.14188/j.1671-8852.2024.0495.

摘要

目的

探究艾司氯胺酮（Esketamine）调控核转录因子红系2相关因子2（Nrf2）通路减轻脓毒症小鼠急性肺损伤（ALI）。

方法

雄性C57BL/6小鼠，随机分成Sham组、盲肠结扎穿孔（CLP）诱导的ALI组和CLP+Esketamine组，每组12只。CLP+Esketamine组在CLP后腹腔注射Esketamine（15 mg/kg）。CLP后24 h对小鼠评分，并记录CLP后7 d体质量。24 h取材，HE染色肺组织并评分，计算肺湿干重比；Western Blot检测各组肺的Nrf2、Kelch样环氧氯丙烷相关蛋白1（Keap1）和血红素加氧酶1（HO⁃1）蛋白水平；ELISA检测小鼠血清IL⁃6、TNF⁃α的水平；免疫荧光染色检测肺紧密连接蛋白。

结果

与Sham组相比，CLP组肺组织损伤加重，肺湿干重比明显升高(

0.001)，血清TNF⁃α及IL⁃6水平升高(

0.000 15)，肺组织紧密连接蛋白减少；肺组织HO⁃1与Nrf2蛋白表达降低(

0.05，

0.001)，Keap1升高(

0.001)。但CLP+Esketamine组能不同程度地改善小鼠状态，减轻炎症和ALI，激活Nrf2信号通路。

结论

Esketamine减轻脓毒症小鼠ALI，可能激活Nrf2信号通路发挥抗氧化作用。

Abstract

Objective

To investigate the ability of Esketamine to attenuate acute lung injury (ALI) in septic mice through the regulation of the nuclear transcription factor red lineage 2⁃related factor 2 (Nrf2) pathway.

Methods

Male C57BL/6 mice were randomized into three groups: Sham

CLP

and CLP+Esketamine. The mouse model of septic ALI was prepared by cecum ligation and perforation (CLP)

and the CLP+Esketamine group was injected peritoneally with Esketamine (15 mg/kg) after the CLP. The mice were scored using murine sepsis score (MSS) after 24 h of modeling

and the body weight were recorded for 7 days. Additionally

24 hours after modeling

the lungs were stained with HE staining to observe the pathological morphology and were scored. The W/D ratio of the lungs was calculated. The expressions of Nrf2

Kelch⁃like ECH⁃associated protein 1 (Keap1) and heme oxygenase⁃1 (HO⁃1) in the lungs were monitored by Western Blot. ELISA assay was adopted to detect the levels of inflammatory cytokines IL⁃6 and TNF⁃α in the serum. Immunofluorescence staining was adopted to detect the expression of lung tight junction proteins.

Results

Compared with those in the Sham group

body temperature and weight decreased in the CLP group. The lung tissue damage in the CLP group was greater

with a higher W/D ratio (

0.001). The levels of TNF⁃α and IL⁃6 in the serum were increased (

0.000 15)

and the tight junction proteins expression decreased. The expression of Keap1 (

0.001)

HO⁃1

and Nrf2 in the lung tissue decreased (

0.05

0.001). Compared with the CLP group

CLP+Esketamine treatment improved the state of mice in various aspects

reduced pulmonary damage

and activated the Nrf2 signaling pathway.

Conclusion

Esketamine attenuates septic ALI in mice

which is related to the activation of the Nrf2 signaling pathway and antioxidant effects.

关键词

Keywords

references

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