右美托咪定通过改善线粒体动力学和耗氧量减轻大鼠脑缺血再灌注损伤的机制  

Mechanism of dexmedetomidine attenuating cerebral ischemia-reperfusion injury in rats by improving mitochondrial dynamics and oxygen consumption

作　　者：杨永红[1,2] 杨帆 王鹏[1,2] YANG Yong-hong;YANG Fan;WANG Peng(Department of Anesthesiology,First People's Hospital of Tianshui City,Tianshui Gansu 741000,China;Department of Neurosurgery,First People's Hospital of Tianshui City,Tianshui Gansu 741000,China)

机构地区：[1]天水市第一人民医院麻醉科,甘肃天水741000 [2]天水市第一人民医院神经外科,甘肃天水741000

出　　处：《临床和实验医学杂志》2022年第17期1801-1805,共5页Journal of Clinical and Experimental Medicine

基　　金：甘肃省科技厅科技支撑项目(编号:1704KFCE087)。

摘　　要：目的探讨右美托咪定(Dex)通过改善线粒体动力学和耗氧量减轻大鼠脑缺血再灌注(CIRI)损伤的机制。方法以24只成年雄性SD大鼠为研究对象,通过中动脉阻塞建立脑缺血再灌注模型,然后按照随机数字表法将其分为对照组(正常大鼠,仅进行假手术处理,n=8),CIRI组(CIRI模型大鼠,n=8)和Dex组(CIRI模型大鼠,给予1 mg·kg^(-1)·d^(-1) Dex治疗,n=8)。通过莫里斯水迷宫测试大鼠认知和记忆功能。通过TTC染色评估大鼠脑梗死体积。通过苏木精和伊红染色和免疫组织化学检测大鼠神经元损伤。通过蛋白质印迹法分析大鼠脑组织中Drp1、Mfn1、Mfn2、细胞质Cytc水平和裂解的caspase-3蛋白表达。通过流式细胞术检测分离线粒体膜电位和活性氧的抵消功能。使用Clark型电极检测脑组织分离线粒体的呼吸耗氧量。结果CIRI组寻找隐藏平台的潜伏期较对照组延长,Dex组寻找隐藏平台的潜伏期较CIRI组缩短,差异均有统计学意义(P<0.05);CIRI组停留在第三象限的时间较对照组缩短,Dex组停留在第三象限的时间较CIRI组延长,差异均有统计学意义(P<0.05)。CIRI组脑梗死体积较对照组增大,Dex组脑梗死体积较CIRI组减小,差异均有统计学意义(P<0.05)。CIRI组海马CA1锥体神经元和NeuN阳性细胞数量较对照组减少,Dex组CA1锥体神经元和NeuN阳性细胞数量较CIRI组增加,差异均有统计学意义(P<0.05)。CIRI组Drp1、细胞质Cytc水平和裂解的caspase-3蛋白表达较对照组升高,Dex组Drp1、细胞质Cytc水平和裂解的caspase-3蛋白表达较CIRI组降低,差异均有统计学意义(P<0.05);CIRI组Mfn1和Mfn2蛋白表达较对照组降低,Dex组Mfn1和Mfn2蛋白表达较CIRI组升高,差异均有统计学意义(P<0.05)。CIRI组线粒体膜电位较对照组降低,Dex组线粒体膜电位较CIRI组升高,差异均有统计学意义(P<0.05)。CIRI组活性氧水平较对照组升高,Dex组活性氧水平较CIRI组降低,差异均有统计学意义(Objective To investigate the mechanism of dexmedetomidine attenuating cerebral ischemia-reperfusion(CIRI)injury in rats by improving mitochondrial dynamics and oxygen consumption.Methods Twenty-four adult male SD rats were used as the research objects,and the cerebral ischemia-reperfusion model was established by middle artery occlusion,then they were divided into control group(normal rats,only sham operation,n=8)and CIRI group(CIRI model rats,n=8)and Dex group(CIRI model rats,given 1 mg·kg^(-1)·d^(-1) Dex treatment,n=8)according to the random number table method.The cognitive and memory functions of rats were tested by morris Water Maze.The volume of cerebral infarction was assessed by TTC staining.Neuron injury was detected by HE staining and immunohistochemistry.The levels of Drp1,Mfn1,Mfn2,cytoplasmic Cytc and the expression of lysed caspase-3 protein in rat brain were analyzed by western blot.Flow cytometry was used to detect the offset function of mitochondrial membrane potential and multiple reactive oxygen species(ROS).Clark electrode was used to measure the oxygen consumption of respiration in isolated mitochondria of brain tissue.Results Compared with the control group,the latency of searching for hidden platforms in the CIRI group was longer than that in the control group,the differences were statistically significant(P<0.05);the latency of finding the hidden platforms in the Dex group was shorter than that in the CIRI group,the differences were statistically significant(P<0.05).The time spent in the third quadrant in the CIRI group was shorter than that in the control group,the Dex group stayed in the third quadrant longer than the CIRI group,the differences were statistically significant(P<0.05).Compared with the control group,the cerebral infarction volume in the CIRI group was increased,and the cerebral infarction volume in the Dex group was decreased compared with the CIRI group,the differences were statistically significant(P<0.05).The numbers of hippocampal CA1 pyramidal neurons and NeuN-posit

关 键 词：大鼠 脑缺血再灌注损伤 右美托咪定 线粒体裂解融合 神经凋亡 

分 类 号：R614[医药卫生—麻醉学]