右美托咪定对大鼠脑组织爆震伤的保护作用及其对介导活性氧/核因子E2相关因子2信号通路的影响  

Protective effect of dexmedetomidine on brain tissue detonation injury in rats and its effect on mediating reactive oxygen species/nuclear factor erythroid 2-related factor 2 signaling pathway

作　　者：雷建军 张贺 Lei Jianjun;Zhang He(Department of Animal Laboratory,General Hospital of Northern Theater Command,Shenyang 110016,China)

机构地区：[1]北部战区总医院实验动物室,沈阳110016

出　　处：《中国临床实用医学》2024年第5期49-54,共6页China Clinical Practical Medicine

基　　金：军队实验动物专项科研课题(SYDW[2018]09号)。

摘　　要：目的探讨右美托咪定(DEX)对大鼠脑组织爆震伤的保护作用及其对介导活性氧(ROS)/核因子E2相关因子2(NRF2)信号通路的影响。方法选取SPF级6周龄大鼠30只,体质量(264.72±13.82)g,体质量范围为250~280 g。采用随机数表法将大鼠随机分为对照组、模型组、模型+DEX组,每组10只。模型组采用自制爆炸装置建立大鼠脑爆震伤模型,模型+DEX组在建立模型2 h后,腹腔注射DEX 20μg/kg,对照组大鼠不做处理。建立模型72 h后对各组大鼠进行改良神经功能损伤评分(mNSS),取大鼠脑组织,采用干湿法检测脑水肿情况;TUNEL免疫荧光染色检测大鼠脑组织神经元细胞凋亡情况;蛋白质免疫印迹法(Western blot)检测各组大鼠脑组织Caspase 3、LC3Ⅱ/Ⅰ、NRF2、HO-1蛋白表达水平;免疫荧光法检测各组大鼠脑组织ROS含量。结果对照组、模型组、模型+DEX组大鼠mNSS评分分别为(0.10±0.04)分、(12.80±2.09)分、(5.90±1.81)分;对照组、模型组、模型+DEX组大鼠脑含水量分别为(79.53±0.31)%、(85.21±1.33)%、(82.10±0.79)%,差异有统计学意义(P<0.05)。模型组大鼠脑组织细胞凋亡高于对照组,模型+DEX组大鼠脑组织细胞凋亡低于对照组,差异有统计学意义(P<0.05)。对照组、模型组、模型+DEX组大鼠脑组织LC3Ⅱ/Ⅰ蛋白表达水平分别为(0.65±0.02)、(1.09±0.05)、(0.94±0.02);Caspase 3蛋白表达水平分别为(0.41±0.02)、(0.97±0.05)、(0.77±0.03);NRF2蛋白表达水平分别为(1.08±0.03)、(0.62±0.03)、(0.96±0.02);HO-1蛋白表达水平分别为(0.90±0.03)、(0.36±0.03)、(0.49±0.03),差异有统计学意义(P<0.05)。模型组大鼠脑组织ROS水平[(38.47±3.04)%]高于对照组[(1.09±0.25)%],模型+DEX组大鼠脑组织ROS水平[(14.71±0.84)%]低于模型组[(38.47±3.04)%],差异有统计学意义(P<0.05)。结论DEX对大鼠脑组织爆震伤具有保护作用,可能与ROS/NRF2信号通路防止神经自噬以改善大鼠脑损伤相关。ObjectiveTo investigate the protective effect of dexmedetomidine(DEX)on brain tissue detonation injury in rats and its effect on mediating reactive oxygen species(ROS)/nuclear factor erythroid 2-related factor 2(NRF2)signaling pathway.MethodsA total of 30 SPF 6-week-old rats,weighing(264.72±13.82)g,ranged from 250 to 280 g,were randomly divided by using the random number table method into control group,model group and model+DEX group,with 10 rats in each group.In the model group,a self-made explosive device was used to establish a rat brain detonation injury model.In the model+DEX group,20μg/kg DEX was intraperitoneally injected 2 h after the model was established,while the control group was not treated.The modified neurological severity scores(mNSS)were assessed in each group of rats at 72 h after model establishment,and the brain tissues were to detect the cerebral edema by wet and dry method.TUNEL immunofluorescence staining was used to detect the apoptosis of neurons in rat brain tissues.The expression levels of Caspase 3,LC3Ⅱ/Ⅰ,NRF2 and HO-1 in brain tissues of rats in each group were detected by Western blot.The ROS content in brain tissue of rats was detected by immunofluorescence method.ResultsThe mNSS of control group,model group and model+DEX group were(0.10±0.04)points,(12.80±2.09)points,(5.90±1.81)points,the brain water content of rats in control group,model group and model+DEX group was(79.53±0.31)%,(85.21±1.33)%,(82.10±0.79)%,and the differences were statistically significant(P<0.05).The apoptosis of brain tissue cells in the model group was higher than that in the control group,the apoptosis of brain tissue cells in the model group was lower than that in the control group,and the differences were statistically significant(P<0.05).The LC3Ⅱ/Ⅰprotein expression levels of control group,model group and model+DEX group were(0.65±0.02),(1.09±0.05),(0.94±0.02);the expression levels of Caspase 3 were(0.41±0.02),(0.97±0.05),(0.77±0.03);the expression levels of NRF2 protein were(1.08±0.

关 键 词：爆震伤 脑组织 活性氧 核因子E2相关因子2 右美托咪定 

分 类 号：R614[医药卫生—麻醉学]