艾司氯胺酮对内毒素性急性肺损伤大鼠肺组织细胞铁死亡的影响

何旋; 吴晓静; 陈鹤翔; 肖兴鹏; 袁敏; 夏中元

doi:10.14188/j.1671-8852.2023.0553

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艾司氯胺酮对内毒素性急性肺损伤大鼠肺组织细胞铁死亡的影响

基础医学研究 | 更新时间：2026-11-05

- 艾司氯胺酮对内毒素性急性肺损伤大鼠肺组织细胞铁死亡的影响
- Effects of esketamine on ferroptosis with endotoxin‑induced acute lung injury in rats
- 武汉大学学报（医学版） 2025年46卷第6期页码：723-728
- 作者机构：
  
  武汉大学人民医院麻醉科湖北武汉 430060
- 作者简介：
  
  何旋，女，1982—，医学博士，主要从事围术期重要脏器保护研究，E‑mail：lumilee@163.com
  夏中元，男，1966—，医学博士，教授，主任医师，博士生导师，主要从事围术期重要脏器保护研究，E‑mail：xiazhongyuan2005@aliyun.com
- 基金信息：
  
  国家自然科学基金资助项目(81970722)
- DOI：10.14188/j.1671-8852.2023.0553
  中图分类号： R563
- 收稿：2023-10-18，
  
  纸质出版：2025-06-25
- 稿件说明：
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何旋,吴晓静,陈鹤翔等.艾司氯胺酮对内毒素性急性肺损伤大鼠肺组织细胞铁死亡的影响[J].武汉大学学报（医学版）,2025,46(06):723-728.

HE Xuan,WU Xiaojing,CHEN Hexiang,et al.Effects of esketamine on ferroptosis with endotoxin‑induced acute lung injury in rats[J].Medical Journal of Wuhan University,2025,46(06):723-728.
何旋,吴晓静,陈鹤翔等.艾司氯胺酮对内毒素性急性肺损伤大鼠肺组织细胞铁死亡的影响[J].武汉大学学报（医学版）,2025,46(06):723-728. DOI： 10.14188/j.1671-8852.2023.0553.

HE Xuan,WU Xiaojing,CHEN Hexiang,et al.Effects of esketamine on ferroptosis with endotoxin‑induced acute lung injury in rats[J].Medical Journal of Wuhan University,2025,46(06):723-728. DOI： 10.14188/j.1671-8852.2023.0553.

摘要

目的

探讨艾司氯胺酮对内毒素性急性肺损伤大鼠肺组织细胞铁死亡的影响。

方法

SPF级健康成年SD大鼠50只，体重200~220 g，8周龄。采用随机数字表法分为5组（

=10）：对照组（Con组），内毒素性急性肺损伤组（ALI组），艾司氯胺酮治疗组（AK组），铁死亡抑制剂治疗组（AF组）和联合治疗组（AKF组）。采用腹腔注射LPS 10 mg·kg

-1

的方法制备大鼠内毒素性急性肺损伤模型。Con组腹腔注射等容量0.9%氯化钠注射液，LPS注射30 min后，AK组腹腔注射艾司氯胺酮10 mg·kg

-1

，AF组腹腔注射铁死亡抑制剂Ferrostatin‑1（Fer‑1）2 mg·kg

-1

，AKF组腹腔注射艾司氯胺酮10 mg·kg

-1

和铁死亡抑制剂Fer‑1 2 mg·kg

-1

。腹腔注射LPS 24 h后，检测动脉血氧合指数（PaO

/FiO

）值、支气管灌洗液（BALF）多核型中性粒细胞（PMN）计数、光镜下观察各组大鼠肺组织HE染色病理学变化并进行肺损伤评分、比色法检测肺组织亚铁离子（Fe

）、谷胱甘肽（GSH）浓度和丙二醛（MDA）、乳酸脱氢酶（LDH）、超氧化物歧化酶（SOD）活性、ELISA法检测肺组织细胞炎症因子TNF‑α、IL‑6水平、Western Blot检测各组大鼠肺组织铁死亡相

关蛋白GPX4、ACSL4和FTH1的表达水平。

结果

与ALI组大鼠比较，各治疗组大鼠肺损伤评分、BALF中PMN计数、肺组织细胞炎症因子TNF‑α、IL‑6水平、Fe

含量、LDH和MDA活性、促铁死亡相关蛋白ACSL4水平明显降低，动脉血PaO

/FiO

值、肺组织GSH含量、SOD活性、抗铁死亡蛋白GPX4和FTH1表达水平则明显升高（

0.05）。

结论

艾司氯胺酮通过降低内毒素性急性肺损伤大鼠肺组织细胞铁死亡水平，减轻肺组织炎症损伤。

Abstract

Objective

To investigate the effects of esketamine on ferroptosis with endotoxin‑induced acute lung injury in rats.

Methods

SPF Male Srague‑Dawley (SD) rats were divided into five groups with the random number table method (

=10): Control group (group Con)

LPS model group (group ALI)

esketamine group (group AK)

Fer‑1 group (group AF)

and esketamine + Fer⁃1 group (group AKF). The rat model of acute lung injury was induced by endotoxin. Rats in Group Con were intraperitoneally injected with an equivalent amount of 0.9% sodium chloride. Rats in the ALI group

AK group

AF group and AKF group were intraperitoneally injected with LPS (10 mg·kg

-1

). Rats in the AK group

AF group and AKF group were respectively intraperitoneally injected with esketamine 10 mg·kg

-1

and/or Fer‑1 2 mg·kg

-1

after injection of LPS 30 minutes. Esketamine and Fer‑1 were administered repeatedly 12 hours after LPS intraperitoneal injection. Lung tissue samples and blood samples were collected after 24 h. We detected PaO

/FiO

ratio in artery blood

PMN in BALF

MDA

LDH

SOD activity and GSH

in lung tissues. The protein expression levels of GPX4

ACSL4 and FTH1 in lung tissues were assayed by using Western Blot

and the levels of TNF‑α and IL‑6 in lung were determined by using ELISA. Pulmonary pathological changes and lung injury scores were determined through HE staining.

Results

Compared with those in group ALI

the PaO

/FiO

lung inj

ury scores

PMN counts in BALF

inflammatory factors TNF‑α and IL‑6 levels

content

LDH

MDA

SOD activities in lung tissue and the levels of ACSL4 were significantly reduced in AK

AF and AKF groups

while the expression levels of GSH

GPX4 and FTH1

on the other hand

were significantly up‑regulated (

0.05).

Conclusion

Esketamine has a protective effect on acute lung injury induced by LPS in rats and the effect may be related to the inhibition of ferroptosis in lung tissue.

关键词

Keywords

references

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