摘要
目的研究布比卡因的神经毒性作用并探讨高压氧预处理的作用。方法实验一:20只雄性SD大鼠随机均分为两组:高压氧组(HBO组)和对照组。所有动物预处理24h后,大鼠经股动脉置管监测血压和动脉血气,股静脉置管泵注布比卡因2mg.kg-1.min-1,计算大鼠出现惊厥、心律失常、心搏停止的布比卡因剂量(mg/kg)。实验二:将体外培养的原代小鼠脊髓神经元随机分成两组:HBO2组和C组,按布比卡因的作用浓度分别设置五个亚组(n=5)。神经元培养至第5天时,依照上述分组设计,HBO2组行HBO预处理,预处理后1h,两组加入不同浓度的布比卡因于37℃,含5%CO2培养箱内培养48h,行MTT比色微量分析测定各孔的细胞活性。上述实验在3批次培养的细胞中重复3次。结果在体实验(实验一)显示,HBO组大鼠出现心律失常时布比卡因剂量与对照组相比差异无统计学意义,但HBO组大鼠出现惊厥和心搏停止时输注的布比卡因剂量明显大于对照组(P<0.05)。体外实验(实验二)表明与正常细胞相比,随着布比卡因浓度升高(0.01%、0.02%、0.04%和0.08%),脊髓神经元的活性显著降低(P<0.01)。不同浓度的布比卡因作用下,HBO2组细胞活性与C组相比差异无统计学意义。结论布比卡因可致剂量依赖性的神经毒性作用,高压氧预处理可减轻布比卡因引起的大鼠中枢神经毒性作用;但其对体外培养的原代培养小鼠脊髓神经元和大鼠心脏的布比卡因毒性无明显保护作用。
Objective To investigate the neurotoxicity of bupivacaine in primary cultured mouse spinal cord neurons in vitro and in rats in vivo, and the effect of preconditioning with hyperbaric oxygen(HBO) on neurotoxicity of bupivacaine. Methods In experiment one, twenty male Sprague-Dawley rats were randomly assigned to one of two groups with 10 rats each. Twenty-four hours after preconditioning,the femoral artery was cannulated for monitoring blood pressure and arterial blood gas. The femoral vein was cannulated for infusion of bupicacaine at a rate of 2 mg · kg^-1 ·min^-1 until asytole occurred. The doses of convulsions,QRS prolongation in ECG (arrhythmia) and asystole were calculated. In experiment two,the cultured mouse spinal cord neurons were randomly assigned to one of two groups: control group and HBO group. The two groups were then divided into five sub-groups with different concentration of bupivacaine(n= 5 holes each). On the fifth day of neuron cultivation, HBO2 group was preconditioned with HBO. At one hour after preconditioning,bupivacaine was added in the holes of both control and HBO2 groups. They were cultured in incubator for 48 h,the viability of the cultured neurons were measured by MTT assay. The experiment was repeated three times. Results Preconditioning with HBO significantly increased the doses of bupivacaine that induced convulsions and cardiac arrest compared to the rats in control group (P 〈 0. 05 ). The viability of cultured neurons treated with bupivacaine at the concentrations of 0. 01% ,0. 02 %, 0. 04 % and 0.08 decreased significantly in a dose-dependent manner compared with that without bupivaine treatment (P〈0. 01 ). Preconditioning with HBO had no influence on the cell viability in cultured spinal neurons treated with bupivacaine. Conclusion Bupivacaine induces neurotoxicity in primary cultured mouse spinal cord neurons in a dose-dependent manner. Preconditioning with HBO attenuates significantly CNS toxicity of bupivacaine in rats. However, it has no alleviative effect on the neurotoxicity of bupivacaine in primary cultured mouse spinal cord neurons in vitro.
出处
《临床麻醉学杂志》
CAS
CSCD
2007年第9期747-750,共4页
Journal of Clinical Anesthesiology
基金
国家自然科学基金项目(项目编号:30571793)
卫生部999中药注射液科研基金项目(项目编号:200312)
关键词
布比卡因
神经毒性
高压氧
预处理
Bupivacaine
Neurotoxcity
Hyperbaric oxygen
Preconditioning