依布硒林减轻DMT1诱导的铁死亡在实验性大鼠蛛网膜下腔出血中的研究

张红霞; 蒋登志; 车旭东; 赵清; 赵俊; 向祥; 何朝晖

doi:10.16016/j.1000-5404.201701128

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依布硒林减轻DMT1诱导的铁死亡在实验性大鼠蛛网膜下腔出血中的研究

基础医学 | 更新时间：2026-01-09

- 依布硒林减轻DMT1诱导的铁死亡在实验性大鼠蛛网膜下腔出血中的研究
- Ebselen relieves ferroptosis induced by divalent mental transporter 1 in rats with subarachnoid hemorrhage
- 第三军医大学学报 2017年39卷第16期页码：1618-1624
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然科学基金面上项目(81371309);重庆市科委自然科学基金(CSTC2012jjA10109);国家临床重点专科建设项目经费资助项目(财社[2011]170号)
- DOI：10.16016/j.1000-5404.201701128
  中图分类号：
- 收稿：2017-01-21，
  
  纸质出版：2017-08-30
- 稿件说明：
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张红霞, 蒋登志, 车旭东, 等. 依布硒林减轻DMT1诱导的铁死亡在实验性大鼠蛛网膜下腔出血中的研究[J]. 第三军医大学学报, 2017,39(16):1618-1624.

Hongxia ZHANG, Dengzhi JIANG, Xudong CHE, et al. Ebselen relieves ferroptosis induced by divalent mental transporter 1 in rats with subarachnoid hemorrhage[J]. Journal of Third Military Medical University, 2017, 39(16): 1618-1624.
张红霞, 蒋登志, 车旭东, 等. 依布硒林减轻DMT1诱导的铁死亡在实验性大鼠蛛网膜下腔出血中的研究[J]. 第三军医大学学报, 2017,39(16):1618-1624. DOI： 10.16016/j.1000-5404.201701128.

Hongxia ZHANG, Dengzhi JIANG, Xudong CHE, et al. Ebselen relieves ferroptosis induced by divalent mental transporter 1 in rats with subarachnoid hemorrhage[J]. Journal of Third Military Medical University, 2017, 39(16): 1618-1624. DOI： 10.16016/j.1000-5404.201701128.

摘要

Abstract

Objective

To investigate the expression of divalent mental transporter 1 (DMT1) and ferroptosis in rats after subarachnoid hemorrhage (SAH) and explore the neuroprotective effect of ebselen in association of inhibiting DMT1 against early brain injury after SAH.

Methods

Rat models of SAH were established by intravascular puncture. Immunofluorescence assay was used to identify the expression and location of DMT1 and glutathione peroxidase 4 (GPX4) in the brain cortex. Ebselen was administered by injection to the SAH. Western blotting was used to detect the expression of DMT and GPX4 at 72 h after the injury or after ebselen intervention. Intracellular iron deposition

iron content

and malonaldehyde (MDA) were measured to evaluate the ferroptosis. Neurological function and brain edema were observed to evaluate the early brain injury.

Results

Immunofluorescence assay indentified DMT1 and GPX4 were both expressed in the cytoplasm of neurons in the brain cortex. Western blot results revealed that the expression level of DMT1 was increased then decreased in 24 h

and kept rising in 48 and 72 h after SAH injury (

0.01)

while that of GPX4 was decreased at 24 h

and then further reduced in 48 and 72 h (

0.01). Compared with the SAH group and vehicle group

injections of 1

2 and 4 mg/kg ebselen decreased the expression of DMT1 but increased that of GPX4

but significant differences were only found in the 2 and 4 mg/kg treatment groups (

0.01). What's more

4 mg/kg ebselen also reduced iron deposition

iron and MDA contents (

0.01)

and elevated GSH content and GPX4 activity (

0.01)

and improved neurological function and augmented brain edema (

0.01).

Conclusion

Ebselen may decrease the intracellular iron transport through inhibiting the expression of DMT1

then decrease the ferroptosis

and thus exert protective effect on the early brain injury in rats after SAH.

关键词

Keywords

references

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