Effects of dexmedetomidine on content of glutamate and expression of NR1 in hippocampus of mice with endotoxemia and the role of cholinergic anti-inflammatory pathway
10.3760/cma.j.cn131073.20190808.00326
- VernacularTitle:右美托咪定对内毒素血症小鼠海马谷氨酸含量及NR1表达的影响及胆碱能抗炎通路在其中的作用
- Author:
Xueyan ZHANG
1
;
Rongqin DAI
;
Huanzhang SHAO
;
Ling YE
;
Wenjie WANG
Author Information
1. 河南省人民医院重症医学科 郑州大学人民医院 450003
- From:
Chinese Journal of Anesthesiology
2020;40(3):362-365
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the effects of dexmedetomidine on the content of glutamate and expression of NR1 in hippocampus of mice with endotoxemia and the role of cholinergic anti-inflammatory pathway.Methods:Eighty clean-grade male C57BL/6 mice, aged 8 weeks, weighing 24-28 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), endotoxemia group (group LPS), dexmedetomidine group (group DEX) and alpha-bungarotoxin (α-BGT) group.Lipopolysaccharide 20 mg/kg was intraperitoneally injected to establish the model of endotoxemia in LPS, DEX and α-BGT groups. Dexmedetomidine 40 μg/kg was intraperitoneally at 15 min before establishing the model in DEX and α-BGT groups.In group α-BGT, alpha-7 nicotinic acetylcholine receptors specific agonist α-BGT 1 μg/kg was intraperitoneally injected at 15 min before injecting dexmedetomidine.Ten mice taken in each group were selected to collect the blood samples from the eyeball and then sacrificed, and hippocampi were isolated.Enzyme-linked immunosorbent assay was used to measure the concentration of serum S100β protein and NSE, and high-performance liquid chromatography was used to determine the content of glutamate in hippocampus.Ten mice in each group were sacrificed at 6 h after establishing the model to detect the expression of NR1 in hippocampus by immumofluorescence method. Results:Compared with group C, the concentrations of serum S100β protein and NSE concentrations and hippocampal glutamate content were significantly increased, and NR1 expression was up-regulated in LPS, DEX and α-BGT groups ( P<0.01). Compared with group LPS, the concentrations of serum S100β protein and NSE concentrations and hippocampal glutamate content were significantly decreased, and NR1 expression was down-regulated in DEX and α-BGT groups ( P<0.01). Compared with group DEX, the concentrations of serum S100β protein and NSE concentrations and hippocampal glutamate content were significantly increased, and NR1 expression was up-regulated in group α-BGT ( P<0.01). Conclusion:The mechanism by which dexmedetomidine alleviates cerebral injury is associated with activating cholinergic anti-inflammatory pathway, decreasing glutamate content and down-regulating NR1 expression in mice with endotoxemia.
