右美托咪定对缺氧缺血性脑损伤新生小鼠的神经保护作用机制研究  

Mechanism of Neuroprotective Effect of Dexmedetomidine on Hypoxic-ischemic Brain Injury in Neonatal Mice

作　　者：吴小军 王日兴[1] 林芳崇 吕有凯 冯奇桃 云天奇 WU Xiaojun;WANG Rixing;LIN Fangchong;LYU Youkai;FENG Qitao;YUN Tianqi(Department of Emergency,the Second Affiliated Hospital of Hainan Medical College,Haikou 570311,China)

机构地区：[1]海南医学院第二附属医院急诊科,海口570311

出　　处：《转化医学杂志》2023年第6期297-302,共6页Translational Medicine Journal

基　　金：海南省卫生健康行业科研项目(21A200233)。

摘　　要：目的 探讨右美托咪定(Dex)对缺氧缺血性脑损伤(HIBD)新生小鼠的神经保护作用及其机制。方法 C57BL/6新生小鼠70只,随机分为假手术组(Sham组)、模型组(HI组)和Dex治疗组(HI+Dex组)、HI+NS-siRNA组、HI+PPARγ-siRNA组、HI+Dex+NS-siRNA组、HI+Dex+PPARγ-siRNA组各10只。除Sham组外,其余均构建新生小鼠HIBD模型,HI+Dex组腹腔注射0.1 mg/kg Dex。Morris水迷宫实验测定Sham组、HI组、HI+Dex组小鼠的学习记忆能力,2,3,5-三苯基四氮唑氯化物染色检测脑梗死体积,TUNEL染色检测脑组织细胞凋亡情况,并检测脑组织活性氧(ROS)水平,Western blotting检测脑组织中Bax、cleaved caspase-3、Bcl-2、SOD2、过氧化物酶体增殖物激活受体(PPARγ)、信号传导与转录激活因子3(STAT3)蛋白表达;分析Dex通过PPAR-γ/STAT3通路对SOD2蛋白表达的影响。结果 与Sham组比较,HI组小鼠脑梗死体积增加,逃避潜伏期延长,平台象限游泳时间百分比降低,脑组织凋亡细胞数量增多,Bax、cleaved caspase-3蛋白表达升高,Bcl-2蛋白表达降低,ROS水平升高,SOD2蛋白水平下降,p-PPARγ和p-STAT3蛋白表达水平升高(P<0.01)。与HI组比较,Dex处理后HIBD新生小鼠脑梗死体积缩小,逃避潜伏期缩短,平台象限游泳时间百分比升高,脑组织凋亡细胞数量减少,Bax、cleaved caspase-3蛋白表达降低,Bcl-2蛋白表达升高,ROS水平降低,SOD2蛋白水平升高,p-PPARγ和p-STAT3蛋白水平升高(P<0.01)。与HI+NS-siRNA组比较,HI+Dex+NS-siRNA组脑组织中p-PPARγ、p-STAT3和SOD2蛋白水平均升高,HI+PPARγ-siRNA组脑组织中p-PPARγ蛋白水平降低(P<0.01);与HI+Dex+NS-siRNA组比较,HI+Dex+PPARγ-siRNA组脑组织中p-PPARγ、p-STAT3和SOD2蛋白水平均降低(P<0.01)。结论 Dex可通过调控PPAR-γ/STAT3通路减轻HIBD新生小鼠脑组织氧化应激损伤,抑制细胞凋亡,进而发挥神经保护作用。Objective To investigate the neuroprotective effect of Dexmedetomidine(Dex)on hypoxic-ischemic brain injury(HIBD)in neonatal mice and its mechanism.Methods C57BL/6 neonatal mice(n=70)were randomly divided into Sham operation group(Sham group,n=10),model group[hypoxic-ischemia(HI)group,n=10]and Dex treatment group(HI+Dex group,n=10),HI+NS-siRNA group(n=10),HI+PPARγ-siRNA group(n=10),HI+Dex+NS-siRNA group(n=10),and HI+Dex+PPARγ-siRNA group(n=10).HIBD models of neonatal mice were constructed in all groups except the Sham group,and the HI+Dex group was intraperitoneally injected with 0.1 mg/kg Dex.The learning and memory ability of mice in Sham group,HI group and HI+Dex group was determined by Morris water maze test.The volume of cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride(TTC)staining,the apoptosis of brain tissue cells was detected by TUNEL staining,and the level of reactive oxygen species(ROS)was detected.Western blotting was used to detect the protein expressions of Bax,cleaved caspase-3,Bcl-2,SOD2,peroxissome proliferator-activated receptor(PPARγ),and signal transduction and transcriptional activator 3(STAT3)in brain tissue.The effect of Dex on the expression of SOD2 protein through PPARγ/STAT3 pathway was analyzed.Results Compared with Sham group,the volume of cerebral infarction in HI group was increased,the escape latency was prolonged,and the percentage of swimming time in the platform quadrant was decreased.The number of apoptotic cells in brain tissue and the expression of Bax and cleaved caspase-3 protein were increased,the expression of Bcl-2 protein was decreased,the ROS level was increased,and the level of SOD2 protein were decreased;the expression levels of p-PPARγand p-STAT3 protein were decreased(P<0.01).Compared with HI group,after Dex treatment,the volume of cerebral infarction was decreased,the escape latency was shortened,and the percentage of swimming time in the platform quadrant was increased.The number of apoptotic cells in brain tissue as well as the express

关 键 词：脑损伤 缺氧缺血 脑 右美托咪定 细胞凋亡 SOD2蛋白 PPARΓ STAT3 新生小鼠 

分 类 号：R-332[医药卫生] R651.15