盐酸右美托咪定对丙泊酚诱导原代培养皮质神经元凋亡的影响  

Effect of Dexmedetomidine on Propofol-induced Neuroapoptosis by Reducing the Mitochondrial Membrane Potential in Primary Cultured Cortical Neurons of Rat

作　　者：李建立[1] 郭洪霞[1] 梁巍[2] 容俊芳[1] 刘锐[3] LI Jianli GUO Hongxia LIANG Wei RONG Junfang LIU Rui(Department of Anesthesiology, Hebei General Hospital, Shijiazhuang 050051, China Department of General Surgery, Hebei General Hospital, Shijiazhuang 050051, China Hebei Chest Hospital, Shijiazhuang 050041, China)

机构地区：[1]河北省人民医院麻醉科,石家庄050051 [2]河北省人民医院普外科,石家庄050051 [3]河北省胸科医院,石家庄050041

出　　处：《医药导报》2016年第11期1164-1168,共5页Herald of Medicine

基　　金：河北省卫生厅指令性课题(ZL20140095)

摘　　要：目的探讨盐酸右美托咪定对丙泊酚诱导原代培养皮质神经元凋亡的影响及其机制。方法将原代培养7 d的大鼠皮质神经元随机分为溶剂对照组(给予等体积20%脂肪乳)、丙泊酚组(丙泊酚终浓度500μmol·L^(-1))和盐酸右美托咪定+丙泊酚组(盐酸右美托咪定终浓度分别为0.001,0.01,0.1,1μmol·L^(-1),丙泊酚终浓度500μmol·L^(-1)),药物处理12 h后,噻唑蓝(MTT)法检测神经元存活率,光学显微镜观察神经元形态,Hoechst33258核染色法检测神经元凋亡率,罗丹明染色检测神经元线粒体膜电位。结果与溶剂对照组比较,丙泊酚组神经元存活率显著下降(P<0.05)。与丙泊酚组比较,盐酸右美托咪定各剂量组神经元存活率升高(P<0.01),作用呈剂量依赖性。与溶剂对照组比较,光镜下丙泊酚组神经元数量明显减少,胞体立体感消失,细胞轮廓不清,神经元轴突断裂。与丙泊酚组比较,盐酸右美托咪定各剂量组神经元形态学损伤明显改善。与溶剂对照组比较,丙泊酚组神经元凋亡率显著上升(P<0.01),线粒体膜电位显著下降(P<0.01)。与丙泊酚组比较,盐酸右美托咪定各剂量组神经元凋亡率显著下降(P<0.01),线粒体膜电位显著上升(P<0.01)。结论盐酸右美托咪定可通过抑制神经元线粒体膜电位下降,减轻丙泊酚所致原代培养皮质神经元凋亡。Objective To investigate the effects and mechanism of dexmedetomidine on propofol-induced neuroapoptosis in primary cultured cortical neurons. Methods After the neurons being cultured for 7 days, they were divided into vehicle control group （equal volume of 20% fat emulsion） ,propofol group（ 500 μmol · L-1） and dexmedetomidine＋propofol group （ dexmedetomidine at 0.001,0.01,0.1 1 μmol · L-1 and propofol at 500 μmol · L-1）.Twelve hours after treatments, neuron viability was measured by MTT assay, neuron structure was analyzed by microscope.Neuroapoptosis was detected by Hoechst33258 staining and mitochondrial membrane potential was measured by the fluorescent dye rhodamine 123 （Rh123）. Results Compared with the vehicle control group,propofol inhibited neuron viability greatly （P〈0.05）. Compared with propofol treatment group, dexmedetomidine increased neuron viability in a dose-dependent manner （P〈0.01）.Lack of three-dimensional sense, faded color and unclear outline were observed, fractured neuron axons or neurons death were also observed in neurons treated by 500 μmol · L-1 propofol. While dexmedetomidine inhibited propofol-induced morphological damage, propofol （500 μmol · L-1） markedly increased the number of apoptotic neurons （P〈0.01） and decreased the mitochondrial membrane potential greatly （P〈 0.01）.Dexmedetomidine （0.1μmol · L-1）significantly decreased the number of apoptotic neurons （P〈0.01） and increased the mitochondrial membrane potential （P〈0.01）. Conclusion Dexmedetomidine exerts its neuroprotective effects against propfol- induced neuroapoptosis by protecting the mitochondrial membrane potential.

关 键 词：右美托咪定 盐酸 丙泊酚 凋亡 皮质神经元 原代培养 线粒体膜电位 

分 类 号：R965[医药卫生—药理学]