Study on Protective Mechanism of Dexmedetomidine on Cerebral Injury in Sepsis Model Rats Based on SIRT 1/ Akt/GSK3β/β-catenin Signaling Pathway
- VernacularTitle:基于SIRT1/Akt/GSK3β/β-catenin信号通路研究右美托咪定对脓毒症模型大鼠脑损伤的保护机制
- Author:
Xiaoliu DONG
1
;
Lihua SONG
1
;
Wei DONG
2
;
Ming GAO
1
;
Xiuqing ZHANG
1
;
Weiran LIU
1
;
Shijun XU
1
;
Tiejun LIU
3
;
Lusha CUI
4
Author Information
1. Dept. of Neurological Rehabilitation，Tangshan People’s Hospital，Hebei Tangshan 063000，China
2. Dept. of Neurosurgery，Tangshan People’s Hospital，Hebei Tangshan 063000，China
3. Dept. of Anesthesiology，the Affiliated Hospital of North China University of Technology，Hebei Tangshan 063000，China
4. Five Wards，Kailuan Mental Health Center，Hebei Tangshan 063000，China
- Publication Type:Journal Article
- Keywords:
Dexmedetomidine;
Sepsis;
Cerebral injury;
Brain protection effect;
SIRT1/Akt/GSK3 β/β-catenin signaling
- From:
China Pharmacy
2020;31(21):2621-2626
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE：To in vestigate the effects of dexmedetomidine （Dex）on SIRT 1/Akt/GSK3β/β-catenin signaling pathway in cerebral injury of sepsis model rats ，and explore the mechanism of its protecitve effect on cerebral injury. METHODS ： A total of 80 male SD rats were randomly divided into sham operation group （Sham group ），sepsis group （CLP group ），CLP+Dex group（10 μg/kg Dex），CLP+Dex+Sirtinol group （10 μg/kg Dex+2 μL/100 g SIRT 1 inhibitor sirtinol ），with 20 mice in each group. Two hours before modeling ，CLP+Dex+Sirtinol group was injected with sirtinol via lateral ventricle. Sepsis model was induced by cecal ligation and perforation in each group （in sham group ，only operation was performed but no ligation was performed）. At 0，3，6 h after modeling ，CLP+Dex group and CLP+Dex+Sirtinol group were given Dex （10 μg/kg） intraperitoneally，Sham group and CLP group were given constant volume of normal saline intraperitoneally. Cerebral tissue water content，Evans blue （EB）content，apoptosis in cerebral cortex ，the levels of IL- 1β and TNF-α in cerebral tissue as well as the protein expression of SIRT 1，p-Akt，p-GSK3β and β-catenin in hippocampus were detected 24 h after last medication. RESULTS ： Compared with Sham group ，cerebral tissue water content ，EB content ，the number of apoptotic cells in cerebral cortex as well as the levels of IL- 1β and TNF-α in cerebral tissue were increased significantly（P＜0.05），while the protein expression of SIRT 1， p-Akt，p-GSK3β and β-catenin in hippocampus were decreased significantly （P＜0.05）. Compared with CLP group ，cerebral tissue water content ，EB content ，the number of apoptotic cells in cerebral cortex as well as the levels of IL- 1β and TNF-α in cerebral tissue were decreased significantly in CLP+Dex group （P＜0.05），while the protein expression of SIRT 1，p-Akt，p-GSK3β and β-catenin in hippocampus were increased significantly （P＜0.05）. Sirtinol could significantly reverse the above-mentioned cerebral protection and factor regulation effects of Dex （P＜0.05）. CONCLUSIONS ：Dex can protect the cerebral tissue of sepsis model rats，which may play an anti-inflammatory and anti-apoptotic role by activating SIRT 1/Akt/GSK3β/β-catenin signaling pathway ，so as to reduce cerebral edema ，protect blood-brain barrier and reduce cerebral injury.
