摘要
目的评价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。方法清洁级雄性C57BL/6小鼠80只,8周龄,体重24~28 g,采用随机数字表法分为4组(n=20):对照组(C组)、内毒素血症组(LPS组)、右美托咪定组(DEX组)和α-银环蛇毒素组(α-BGT组)。LPS组、DEX组和α-BGT组分别腹腔注射LPS 20 mg/kg制备内毒素血症模型;DEX组和α-BGT组于造模前15 min时腹腔注射右美托咪定40μg/kg;α-BGT组于注射右美托咪定前15 min腹腔注射α7nAchR特异性拮抗剂α-银环蛇毒素1μg/kg。造模后6 h时,每组取10只小鼠,眼球取血样后处死,分离海马组织,采用ELISA法测定血清S100β蛋白和NSE浓度,采用高效液相色谱法测定海马谷氨酸含量。造模后6 h时,每组处死10只小鼠,采用免疫荧光法检测海马NR1表达。结果与C组比较,LPS组、DEX组和α-BGT组血清S100β蛋白和NSE浓度升高,海马谷氨酸含量和NR1表达水平升高(P<0.01);与LPS组比较,DEX组和α-BGT组血清S100β蛋白和NSE浓度降低,海马谷氨酸含量和NR1表达水平降低(P<0.01);与DEX组比较,α-BGT组血清S100β蛋白和NSE浓度升高,海马谷氨酸含量和NR1表达水平升高(P<0.01)。结论右美托咪定减轻内毒素血症小鼠脑损伤的机制与激活胆碱能抗炎通路,降低谷氨酸含量,下调NR1表达有关。
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 andα-BGT groups.Dexmedetomidine 40μg/kg was intraperitoneally at 15 min before establishing the model in DEX andα-BGT groups.In groupα-BGT,alpha-7 nicotinic acetylcholine receptors specific agonistα-BGT 1μg/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 S100βprotein 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 S100βprotein and NSE concentrations and hippocampal glutamate content were significantly increased,and NR1 expression was up-regulated in LPS,DEX andα-BGT groups(P<0.01).Compared with group LPS,the concentrations of serum S100βprotein and NSE concentrations and hippocampal glutamate content were significantly decreased,and NR1 expression was down-regulated in DEX andα-BGT groups(P<0.01).Compared with group DEX,the concentrations of serum S100βprotein and NSE concentrations and hippocampal glutamate content were significantly increased,and NR1 expression was up-regulated in groupα-BGT(P<0.01).Conclusion The mechanism b
作者
张雪艳
代荣钦
邵换璋
叶岭
王文杰
Zhang Xueyan;Dai Rongqin;Shao Huanzhang;Ye Ling;Wang Wenjie(Department of Intensive Care Unit,Henan Provincial People′s Hospital,People′s Hospital of Zhengzhou University,Zhengzhou 450003,China)
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2020年第3期362-365,共4页
Chinese Journal of Anesthesiology
基金
河南省科技攻关计划项目(142102310403)。
