Dexmedetomidine protects cerebral ischemia-reperfusion injury by inhibiting microglial activation

Tongju YANG; Kai WANG; Zhen WANG; Liyong CHEN

doi:10.16016/j.1000-5404.201808004

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Dexmedetomidine protects cerebral ischemia-reperfusion injury by inhibiting microglial activation

Basic Medicine | 更新时间：2026-01-09

- Dexmedetomidine protects cerebral ischemia-reperfusion injury by inhibiting microglial activation
- Journal of Third Military Medical University Vol. 40, Issue 23, Pages: 2197-2203(2018)
- 作者机构：
  
  400042 重庆, 陆军军医大学(第三军医大学)第三附属医院(野战外科研究所)麻醉科
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.201808004
  CLC： R743.31;R965;R971.3
- Received：01 August 2018，
  
  Revised：2018-09-25，
  
  Published：15 December 2018
- 稿件说明：
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Tongju YANG, Kai WANG, Zhen WANG, et al. Dexmedetomidine protects cerebral ischemia-reperfusion injury by inhibiting microglial activation[J]. Journal of Third Military Medical University, 2018, 40(23): 2197-2203.
DOI：

Tongju YANG, Kai WANG, Zhen WANG, et al. Dexmedetomidine protects cerebral ischemia-reperfusion injury by inhibiting microglial activation[J]. Journal of Third Military Medical University, 2018, 40(23): 2197-2203. DOI： 10.16016/j.1000-5404.201808004.

摘要

目的

探讨右美托咪定(dexmedetomidine

Dex)对局灶性脑缺血再灌注(ischemia-reperfusion

I/R)损伤的保护作用及其机制。

方法

采用大鼠大脑中动脉栓塞(middle cerebral artery occlusion

MCAO)模型。取60只SD雄性大鼠按随机数字表法分为3组(

=20):Sham组、I/R组和Dex+I/R组。各组评估神经功能情况

检测梗死侧大脑皮层病理改变、半暗带神经细胞凋亡率、小胶质细胞活化率及皮层匀浆TNF-α水平。建立小胶质细胞氧糖剥夺/复氧(oxygen glucose deprivation/reoxygenation

OGD/R)模型。将培养的BV2小胶质细胞分为Control组、OGD/R组和1 μmol/L Dex+OGD/R组、10 μmol/L Dex+OGD/R组。检测细胞上清液TNF-α浓度

及细胞内CD68、NF-κB p65、p-NF-κB p65蛋白表达情况。

结果

与I/R组比较

Dex+I/R组神经功能评分降低(

0.05)

大脑皮层病理损伤减轻

半暗带神经细胞凋亡率降低(

0.05)

小胶质细胞活化率降低(

0.05)

大脑皮层匀浆TNF-α浓度降低(

0.05)。与OGD/R组比较

1 μmol/L Dex+OGD/R组、10 μmol/L Dex+OGD/R组细胞上清液TNF-α浓度降低(

0.05)

10 μmol/L Dex+OGD/R组细胞内CD68、p-NF-κB p65表达减少(

0.05)。

结论

右美托咪定通过抑制小胶质细胞活化减轻脑缺血再灌注损伤发挥脑保护作用

可能与其抑制小胶质细胞NF-κB通路有关。

Abstract

Objective

To investigate the protective effect and underlying mechanism of dexmedetomidine (Dex) on focal cerebral ischemia-reperfusion (I/R) injury.

Methods

Sixty male Sprague-Dawley rats were randomly divided into sham group

I/R group and Dex treatment group

with 20 animals in each group. Rat middle cerebral artery occlusion (MCAO) model was adopted. The neurological function was evaluated

and the pathological changes

apoptotic ratio of nerve cells in penumbra

activation ratio of microglia in penumbra and level of TNF-α in the infarct cerebral cortical homogenate of each group were detected. Mouse microglial BV2 cells were randomly divided into control group

oxygen glucose deprivation/reoxygenation (OGD/R) group

1 μmol/L Dex+OGD/R group

10 μmol/L Dex+OGD/R group. The concentration of TNF-α in the supernatant and the protein levels of CD68

NF-κB p65 and p-NF-κB p65 in the BV2 cells were detected.

Results

Compared with the I/R group

the neurological function score was reduced (

0.05)

pathological damage in the cerebral cortex was attenuated

and the apoptosis ratio of nerve cells (

0.05)

activation ratio of microglia (

0.05) and concentration of TNF-α (

0.05) in the cerebral cortical homogenate were decreased in the Dex+I/R group. Compared with the OGD/R group

Dex treatment decreased the concentration of TNF-α in the supernatant (

0.05)

but only 10 μmol/L Dex decreased the expression of CD68 and p-NF-κB p65 in the BV2 cells (

0.05).

Conclusion

Dex exerts protective effect against cerebral I/R injury by inhibiting microglial activation

which may be related to the inhibition of NF-κB signaling pathway in microglia.

关键词

Keywords

references

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