天津医药

天津医药 ›› 2016, Vol. 44 ›› Issue (4): 430-433.doi: 10.11958/58574

• 细胞与分子生物学 • 上一篇    下一篇

右美托咪定对布比卡因所致神经细胞毒性的保护作用

陈根殷，王旭光△   

  1. 湛江市，广东医学院附属医院（邮编524001）
  • 收稿日期:2015-03-13 修回日期:2015-11-01 出版日期:2016-04-15 发布日期:2016-05-20
  • 通讯作者: △通讯作者 E-mail： marvin009@126.com E-mail:marvin1974@163.com
  • 作者简介:陈根殷（1973），女，主任医师，主要从事麻醉药物基础研究

Protective effects of dexmedetomidine on bupivacaine-induced neurotoxicity

CHEN Genyin, WANG Xuguang△   

  1. The Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China
  • Received:2015-03-13 Revised:2015-11-01 Published:2016-04-15 Online:2016-05-20
  • Contact: △Corresponding Author E-mail： marvin009@126.com E-mail:marvin1974@163.com

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摘要： 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 1 000 µmol/L 布比卡因； 50、 200 µmol/L 右美托咪定浓度组细胞中加入 1 000 µmol/L 布比卡因后， 再分别加入 50、 200 µmol/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 1 000 µmol/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、 200 µmol/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， 200 µmol/L 右美托咪定的变化较 50 µmol/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。

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

Abstract: Abstract: Objective To investigate the protective effects of dexmedetomidine on bupivacaine-induced neurotoxicity. Methods Mouse neuroblastoma cell line N2a 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. The cells 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 N2a cells were detected by flow cy⁃ tometry. Results The cell viabilities were significantly decreased after being treated with 1 000 µmol/L bupivacaine, MMP was 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 the cell viability and MMP, but decrease in apoptotic rate and levels of ROS and Caspase-3. These effects were more significant in 200 µmol/L dexmedetomidine group than those of 50 µmol/L dexmedetomidine group. Conclusion Dexmedetomidine at⁃ tenuates bupivacaine-induced cytotoxicity of N2a cells, which may be related with the inhibition of ROS, the decrease in MMP and Caspase-3, and inhibiting appotosis in N2a cells.

Key words: dexmedetomidine, bupivacaine, apoptosis, reactive oxygen species, flow cytometry, neurotoxicity, mitochondrial membrane potential