右美托咪定对布比卡因所致神经细胞毒性的保护作用  

Protective effects of dexmedetomidine on bupivacaine-induced neurotoxicity

作　　者：陈根殷[1] 王旭光[1] 

机构地区：[1]广东医学院附属医院,湛江市524001

出　　处：《天津医药》2016年第4期430-433,共4页Tianjin Medical Journal

摘　　要：目的探讨右美托咪定对布比卡因所致神经细胞毒性的保护作用。方法体外培养小鼠神经母细胞瘤细胞株N2a细胞,取对数期细胞分为4组:对照组细胞培养液不加任何药物;布比卡因组细胞中加入1 000μmol/L布比卡因;50、200μmol/L右美托咪定浓度组细胞中加入1 000μmol/L布比卡因后,再分别加入50、200μmol/L右美托咪定。各组细胞加入药物后继续培养24 h,以MTT法检测细胞存活率;流式细胞术检测细胞凋亡、活性氧(ROS)水平、线粒体膜电位及Caspase-3的表达。结果在1 000μmol/L布比卡因作用下,各药物组N2a细胞的存活率明显降低,同时线粒体膜电位显著下降,而细胞的凋亡率、胞内ROS水平和Caspase-3表达则显著升高;50、200μmol/L右美托咪定可抑制布比卡因引起的N2a细胞毒性,使细胞的存活率及线粒体膜电位均明显升高,同时降低细胞的凋亡率、胞内ROS水平和Caspase-3表达,200μmol/L右美托咪定的变化较50μmol/L更为明显。结论右美托咪定可减轻布比卡因对N2a细胞的毒性作用,其可能是通过抑制ROS的生成、改变线粒体膜电位、降低Caspase-3的表达,从而抑制细胞的凋亡来实现的。Objective To investigate the protective effects of dexmedetomidine on bupivacaine-induced neurotoxicity.Methods Mouse neuroblastoma cell line N2 a cells were divided into four groups. The cells in the control group were incu-bated with no drug adding while the cells in bupivacaine group were treated with 1 000 μmol/L bupivacaine for 24 h. Thecells in the group Dex1 and Dex2 were incubated with 1 000 μmol/L bupivacaine and 50 μmol/L, 200 μmol/L dexmedetomi-dine for 24 h respectively. MTT assay was used to evaluate the cell viability. The reactive oxygen species（ROS） activity, mito-chondrial membrane potential（MMP）, the expression of Caspase-3 and apoptotic rate of N2 a cells were detected by flow cy-tometry. Results The cell viabilities were significantly decreased after being treated with 1 000 μmol/L bupivacaine, MMPwas also significantly decreased, and apoptotic rates, levels of ROS and Caspase-3 were significantly increased. The bupiva-caine-induced cytotoxicity was inhibited by dexmedetomidine（50 and 200 μmol/L）, which resulted in the increase in thecell viability and MMP, but decrease in apoptotic rate and levels of ROS and Caspase-3. These effects were more significantin 200 μmol/L dexmedetomidine group than those of 50 μmol/L dexmedetomidine group. Conclusion Dexmedetomidine at-tenuates bupivacaine-induced cytotoxicity of N2 a cells, which may be related with the inhibition of ROS, the decrease inMMP and Caspase-3, and inhibiting appotosis in N2 a cells.

关 键 词：右美托咪定 布比卡因 细胞凋亡 活性氧 流式细胞术 神经损伤 线粒体膜电位 

分 类 号：R614.1[医药卫生—麻醉学]