[1]杨桐榉,王凯,王震,等.右美托咪定抑制小胶质细胞活化发挥脑保护作用的实验研究[J].第三军医大学学报,2018,40(23):2197-2203.
 YANG Tongju,WANG Kai,WANG Zhen,et al.Dexmedetomidine protects cerebral ischemia-reperfusion injury by inhibiting microglial activation[J].J Third Mil Med Univ,2018,40(23):2197-2203.
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右美托咪定抑制小胶质细胞活化发挥脑保护作用的实验研究(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
40卷
期数:
2018年第23期
页码:
2197-2203
栏目:
基础医学
出版日期:
2018-12-15

文章信息/Info

Title:
Dexmedetomidine protects cerebral ischemia-reperfusion injury by inhibiting microglial activation
作者:
杨桐榉王凯王震陈力勇
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
Author(s):
YANG Tongju WANG Kai WANG Zhen CHEN Liyong

Department of Anesthesiology, Institute of Surgery Research, Third Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, China

关键词:
右美托咪定小胶质细胞脑缺血再灌注脑保护
Keywords:
dexmedetomidine microglia cerebral ischemia/reperfusion brain protection
分类号:
R743.31;R965;R971.3
文献标志码:
A
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(n=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(P<0.05),大脑皮层病理损伤减轻,半暗带神经细胞凋亡率降低(P<0.05),小胶质细胞活化率降低(P<0.05),大脑皮层匀浆TNF-α浓度降低(P<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(P<0.05),10 μmol/L Dex+OGD/R组细胞内CD68、p-NF-κB p65表达减少(P<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:

ObjectiveTo investigate the protective effect and underlying mechanism of dexmedetomidine (Dex) on focal cerebral ischemia-reperfusion (I/R) injury.  MethodsSixty 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. ResultsCompared with the I/R group, the neurological function score was reduced (P<0.05), pathological damage in the cerebral cortex was attenuated, and the apoptosis ratio of nerve cells (P<0.05), activation ratio of microglia (P<0.05) and concentration of TNF-α (P<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 (P<0.05), but only 10 μmol/L Dex decreased the expression of CD68 and p-NF-κB p65 in the BV2 cells (P<0.05). ConclusionDex 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.

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更新日期/Last Update: 2018-12-19