艾司氯胺酮对创伤性脑损伤大鼠神经元损伤炎症及AMPK/NF-κB信号通路的影响  

Effects of Esketamine on Neuronal Damage Inflammation and AMPK/NF-κB Signaling Pathway in Rats with Traumatic Brain Injury

作　　者：刘璇 滕金亮[1] 袁莉 景巍 李国利[1] 訾聪娜[1] LIU Xuan;TENG Jinliang;YUAN Li(The First Hospital Affiliated to Hebei North University,Hebei Zhangjiakou 075061,China)

机构地区：[1]河北北方学院附属第一医院,河北张家口075061

出　　处：《河北医学》2023年第5期710-716,共7页Hebei Medicine

基　　金：河北省政府资助临床医学人才培养项目,(编号:冀卫办科教[2021]1号)。

摘　　要：目的:探讨艾司氯胺酮对创伤性脑损伤(TBI)大鼠神经元损伤、炎症及单磷酸腺苷活化蛋白激酶(AMPK)/核因子-κB(NF-κB)信号通路的影响。方法:将大鼠按照随机数表法分为假手术组、模型组、艾司氯胺酮组(50mg/kg)、AMPK抑制剂组(20mg/kg)、艾司氯胺酮+AMPK抑制剂组(50mg/kg+20mg/kg),除假手术组外,其余各组建立TBI大鼠模型,各组给予相应干预7d。采用改良神经功能缺损评分(mNSS)评估大鼠神经功能;酶联免疫吸附法检测血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平;HE染色观察大鼠损伤灶周围脑组织病变状况;尼氏染色观察大鼠损伤灶周围脑组织神经元损伤状况;TUNEL检测大鼠损伤灶周围脑组织神经元凋亡情况;蛋白印迹法检测大鼠损伤灶周围脑组织中AMPK/NF-κB通路蛋白表达。结果:与假手术组相比,模型组大鼠损伤灶周围脑组织出现严重病变、神经元损伤严重,mNSS评分、血清IL-6、TNF-α、神经元凋亡数、磷酸化NF-κB p65(p-NF-κB p65)/NF-κB p65蛋白表达显著升高,磷酸化AMPK(p-AMPK)/AMPK蛋白表达显著降低(P<0.05)。与模型组相比,艾司氯胺酮组大鼠损伤灶周围脑组织病理状况和神经元损伤得到改善,mNSS评分、血清IL-6、TNF-α、神经元凋亡数、p-NF-κB p65/NF-κB p65蛋白表达显著降低,p-AMPK/AMPK蛋白表达显著升高(P<0.05),AMPK抑制剂组大鼠损伤灶周围脑组织病变、神经元损伤加重,mNSS评分、血清IL-6、TNF-α、神经元凋亡数、p-NF-κB p65/NF-κB p65蛋白表达显著升高,p-AMPK/AMPK蛋白表达显著降低(P<0.05)。艾司氯胺酮+AMPK抑制剂组上述各指标变化介于艾司氯胺酮组和AMPK抑制剂组之间。结论:艾司氯胺酮可减轻TBI大鼠神经元损伤和炎症反应,可能与调控AMPK/NF-κB信号通路有关。Objective:To investigate the effects of esketamine on neuronal injury,inflammation and adenosine monophosphate activated protein kinase(AMPK)/nuclear factor-κB(NF-κB)signaling pathway in rats with traumatic brain injury(TBI).Methods:According to the random number table,the rats were divided into sham operation group,model group,esketamine group(50 mg/kg),AMPK inhibitor group(20 mg/kg),and esketamine+AMPK inhibitor group(50 mg/kg+20 mg/kg).TBI rat models were established in groups except the sham operation group,and each group was given corresponding intervention for 7 days.Modified neurological severity score(mNSS)was used to evaluate the neural function of rats;serum levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay;HE staining was used to observe the pathological changes of the brain tissue around the lesion;Nissner staining was used to observe the damage of neurons in the brain surrounding the lesion;TUNEL was used to detect the apoptosis of neurons in the brain surrounding the lesion;detection of AMPK/NF-κB pathway protein expression in the brain tissue around the injured focus of rats by Western blot.Results:Compared with the sham group,rats in the model group showed severe lesions and neuronal damage around the foci of injury.mNSS score,serum IL-6,TNF-α,neuronal apoptosis number,phosphorylated NF-κB p65(p-NF-κB p65)/NF-κB p65 protein expression were significantly increased,and phosphorylated AMPK(p-AMPK)/AMPK protein expression was significantly decreased(P<0.05).Compared with the model group,the brain tissue pathological condition and neuronal damage around the injury foci were improved in the esketamine group.mNSS score,serum IL-6,TNF-α,neuronal apoptosis number,p-NF-κB p65/NF-κB p65 protein expression was significantly reduced and p-AMPK/AMPK protein expression was significantly increased in the AMPK inhibitor group(P<0.05).In rats,brain tissue lesions and neuronal damage around the injury foci were aggravated,and mNSS score,seru

关 键 词：艾司氯胺酮 创伤性脑损伤 神经元损伤 单磷酸腺苷活化蛋白激酶/核因子-κB通路 

分 类 号：R651.15[医药卫生—外科学]