Protective effect of dexmedetomidine against diabetic hyperglycemia-exacerbated cerebral ischemia/reperfusion injury: An in vivo and in vitro study

被引：53
作者：
Chen, Lingyang [1 ,2 ]
Cao, Jianbin [1 ,2 ]
Cao, Donghang [1 ,2 ]
Wang, Mingcang [1 ,2 ]
Xiang, Haifei [3 ]
Yang, Yanqing [1 ,2 ]
Ying, Tingting [1 ,2 ]
Cong, Haitao [1 ,2 ]
机构：
[1] Wenzhou Med Univ, Affiliated Taizhou Hosp, Dept Anesthesiol, 150 Ximen St, Linhai 317000, Zhejiang, Peoples R China
[2] Taizhou Enze Med Ctr Grp, Taizhou Hosp Zhejiang Prov, Dept Anesthesiol, Linhai 317000, Zhejiang, Peoples R China
[3] Taizhou Enze Med Ctr Grp, Enze Hosp, Dept Anesthesiol, Linhai 317000, Zhejiang, Peoples R China
来源：
LIFE SCIENCES | 2019年 / 235卷
关键词：
Dexmedetomidine; Diabetic hyperglycemia-exacerbated cerebral; ischemia/reperfusion injury; Nuclear factor of activated T-cells 5; Sirtuin; 1; NF-E2-related factor 2; NF-KAPPA-B; OXIDATIVE STRESS; ISCHEMIC-STROKE; SIGNALING PATHWAY; ERK1/2; PATHWAYS; NUCLEAR FACTOR; BRAIN; SIRT1; NEUROPROTECTION; EXPRESSION;
D O I：
10.1016/j.lfs.2019.116553
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Aims: Dexmedetomidine (Dex) has been noted to have neuroprotective effect against cerebral ischemia-reperfusion (I/R) injury. However, the effect of Dex in diabetic hyperglycemia-exacerbated cerebral I/R injury and its underlying mechanism remain unclear. Main methods: The infarct volume and brain edema were evaluated by 2,3,5-triphenyltetrazolium chloride staining and standard wet-dry method. Modified neurological severity score was utilized to assess the neurological deficits. The oxidative stress and inflammation were evaluated by detecting reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and cell count kit-8 were applied to measure cell apoptosis and viability. Key findings: Dex treatment reduced infarct volume, decreased brain water content and improved neurological deficit in middle cerebral artery occlusion/reperfusion (MCAO/R) mice. Dex treatment reduced the levels of ROS, MDA, TNF-alpha and IL-1 beta in the entire middle cerebral artery territory of diabetic mice subjected to MCAO/R, as well as in primary culture of mouse hippocampal neurons stimulated with 50 mM glucose and oxygen glucose deprivation/reperfusion. Dex treatment inhibited neuronal apoptosis induced by diabetic hyperglycemia-exacerbated cerebral I/R injury. Dex upregulated nuclear factor of activated T-cells 5 (NFAT5) and Sirtuin 1 (SIRT1) expression, induced NF-E2-related factor 2 (Nrf2) translocation from cytoplasm to nucleus and inhibited the acetylation of Nrf2. However, these changes triggered by Dex treatment were abrogated by NFAT5 knockdown. Significance: Dex protects against diabetic hyperglycemia-exacerbated cerebral I/R injury through attenuation of oxidative stress, inflammation and apoptosis. The underlying mechanism is at least the NFAT5/SIRT1/Nrf2 signaling pathway dependent.
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页数：11
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