资源类型:
期刊
WOS体系:
Article
Pubmed体系:
Journal Article
收录情况:
◇ SCIE
◇ 统计源期刊
◇ CSCD-C
◇ 卓越:梯队期刊
文章类型:
论著
机构:
[1]Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
[2]Department of Anesthesiology, First Affiliated Hospital of Kunming Medical University, No.1 School of Clinical Medicine, Kunming Medical University, Kunming 650011, China.
外科科室
麻醉手术科(医技)
昆明医科大学附属第一医院
ISSN:
1672-9145
摘要:
Stroke is the second leading cause of death and long-term disability worldwide, which lacks effective treatment. Perioperative stroke is associated with much higher rates of mortality and disability. The neuroprotective role of dexmedetomidine (Dex), a highly selective agonist of alpha2-adrenergic receptor, has been reported in a stroke rat model, and it was found that pretreatment of Dex before stroke could alleviate blood-brain barrier (BBB) breakdown. However, the underlying mechanisms are still unknown. As the brain endothelial cells are the main constituents of BBB and in high demand of energy, mitochondrial function of endothelial cells plays an important role in the maintenance of BBB. Given that dynamin-related protein 1 (Drp1) is a protein mediating mitochondrial fission, with mitochondrial fusion that balances mitochondrial morphology and ensures mitochondria function, the present study was designed to investigate the possible role of Drp1 in endothelial cells involved in the neuroprotective effects of Dex in ischemic stroke. Our results showed that preconditioning with Dex reduced infarction volume, alleviated brain water content and BBB damage, and improved neurological scores in middle cerebral artery occlusion rats. Meanwhile, Dex enhanced cell activity and decreased cell apoptosis in oxygen-glucose deprivation human brain microvascular endothelial cells in vitro. These protective effects of Dex were correlated with the mitochondrial morphology integrality of endothelial cells, mediated by increased phosphorylation of serine 637 in Drp1, and could be reversed by α2-adrenergic receptor antagonist Yohimbine and AMP-activated protein kinase inhibitor Compound C. These findings suggest new molecular pathways involved in the neuroprotective effects of Dex in ischemic stroke. As Dex is routinely used as a sedative drug clinically, our findings provide molecular evidence that it has perioperative neuroprotection from ischemic stroke.© The Author(s) 2021. Published by Oxford University Press on behalf of the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
基金:
This work was supported by the grants from Shanghai Municipal
Key Clinical Specialty (No. shslczdzk03601), the Innovation
Program of Shanghai Municipal Education Commission (No. 2019-
01-07-00-01-E00074), the National Natural Science Foundation of
China (Nos. 81970478 and 32030043), and the Natural Science
Foundation of the Shanghai Committee of Science and Technology
Commission (No. 20ZR1433400).
基金编号:
No. shslczdzk03601
被引次数:
11
WOS:
WOS:000696253200007
PubmedID:
34244711
中科院(CAS)分区:
出版当年[2022]版:
大类
|
3 区
生物学
小类
|
3 区
生物物理
3 区
生化与分子生物学
最新[2023]版:
大类
|
2 区
生物学
小类
|
2 区
生物物理
3 区
生化与分子生物学
JCR分区:
出版当年[2021]版:
Q2
BIOPHYSICS
Q3
BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版:
Q1
BIOPHYSICS
Q2
BIOCHEMISTRY & MOLECULAR BIOLOGY
影响因子:
3.3
最新[2023版]
3.4
最新五年平均
3.511
出版当年[2021版]
3.893
出版当年五年平均
3.848
出版前一年[2020版]
3.7
出版后一年[2022版]
第一作者:
Zhou Wei
第一作者机构:
[1]Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
共同第一作者:
Zhang Yunchun
通讯作者:
Wang Zhenhong;Yu Weifeng
推荐引用方式(GB/T 7714):
Zhou Wei,Zhang Yunchun,Jiao Yingfu,et al.Dexmedetomidine maintains blood-brain barrier integrity by inhibiting Drp1-related endothelial mitochondrial dysfunction in ischemic stroke.[J].ACTA BIOCHIMICA ET BIOPHYSICA SINICA.2021,53(9):1177-1188.doi:10.1093/abbs/gmab092.
APA:
Zhou Wei,Zhang Yunchun,Jiao Yingfu,Yin Wen,Dong Haiping...&Yu Weifeng.(2021).Dexmedetomidine maintains blood-brain barrier integrity by inhibiting Drp1-related endothelial mitochondrial dysfunction in ischemic stroke..ACTA BIOCHIMICA ET BIOPHYSICA SINICA,53,(9)
MLA:
Zhou Wei,et al."Dexmedetomidine maintains blood-brain barrier integrity by inhibiting Drp1-related endothelial mitochondrial dysfunction in ischemic stroke.".ACTA BIOCHIMICA ET BIOPHYSICA SINICA 53..9(2021):1177-1188