Role of mitochondrial fusion and fission in protective effects of dexmedetomidine against cerebral ischemia/reperfusion injury in mice.
10.12122/j.issn.1673-4254.2020.04.03
- Author:
Gang LIU
1
;
Yunzheng MEN
2
;
Xuhui TONG
2
;
Xueru WANG
2
;
Miao HU
2
;
Mujun JIANG
2
;
Zhipeng SUN
3
;
Shuying DONG
2
Author Information
1. Department of Anesthesiology, First Affiliated Hospital, Bengbu Medical College, Bengbu 233030, China.
2. Department of Pharmacology, School of Pharmacy, Bengbu Medical College, Bengbu 233030, China.
3. Grade 2018, School of Pharmacy, Bengbu Medical College, Bengbu 233030, China.
- Publication Type:Journal Article
- Keywords:
AMPK signaling pathway;
cerebral ischemia reperfusion;
dexmedetomidine;
mitochondrial fusion and fission
- MeSH:
Animals;
Brain Ischemia;
Dexmedetomidine;
Male;
Mice;
Mice, Inbred ICR;
Mitochondrial Dynamics;
Reperfusion Injury
- From:
Journal of Southern Medical University
2020;40(4):463-468
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the protective effects of dexmedetomidine (DEX) against cerebral ischemia/reperfusion (I/R) injury in mice and its relation with mitochondrial fusion and fission.
METHODS:Male ICR mice were randomly divided into sham-operated group, I/R group, I/R+DEX group and I/R+DEX+dorsomorphin group. Mouse models of cerebral I/R injury were established by modified thread occlusion of the middle cerebral artery. DEX (50 μg/kg) was injected intraperitoneally at 30 min before cerebral ischemia, which lasted for 1 h followed by reperfusion for 24 h. The neurobehavioral deficits of the mice were evaluated based on Longa's scores. The volume of cerebral infarction was detected by TTC staining. The changes in mitochondrial morphology of the brain cells were observed with transmission electron microscopy. Western blotting was performed to detect the expressions of phosphorylated AMP-activated protein kinase (p-AMPK), mitochondrial fusion protein (Mfn2) and mitochondrial fission protein (p-Drp1) in the brain tissues.
RESULTS:DEX pretreatment significantly reduced the neurobehavioral score and the percent volume of cerebral infarction in mice with cerebral I/R injury. Treatment with dorsomorphin (an AMPK inhibitor) in addition to DEX significantly increased the neurobehavioral score and the percent volume of cerebral infarction in the mouse models. Transmission electron microscopy showed that DEX obviously reduced mitochondrial damage caused by cerebral I/R injury and restored mitochondrial morphology of the brain cells, and such effects were abolished by dorsomorphin treatment. Western blotting showed that DEX pretreatment significantly increased the expressions of p-AMPK and Mfn2 protein and decreased the expression of p-Drp1 protein in the brain tissue of the mice, and these changes were also reversed by dorsomorphin treatment.
CONCLUSIONS:Preconditioning with DEX produces protective effects against cerebral I/R injury in mice possibly by activating AMPK signaling to regulate mitochondrial fusion and fission in the brain cells.
