静脉注射神经节苷脂对大鼠鞘内注入布比卡因脊神经毒性的治疗作用  

Therapeutic function of intravenous monosialoganglioside GM-1on neurotoxicity of intrathecally adminis-tered bupivacaine in rats

作　　者：吉杰梅[1] 陆华良[1] 吴周晏 赖坚[1] 刘敬臣[1] 

机构地区：[1]广西医科大学第一附属医院麻醉科,南京市530021

出　　处：《临床麻醉学杂志》2014年第7期705-708,共4页Journal of Clinical Anesthesiology

摘　　要：目的探讨静脉注射单唾液酸神经节苷脂(GM-1)对大鼠鞘内注入布比卡因脊神经毒性的治疗作用。方法 108只雄性SD大鼠随机均分为三组:假手术组(sham组)、生理盐水组(saline组)和GM-1组。saline组和GM-1组行鞘内置管,间隔1.5小时重复注入5%布比卡因0.12μl/g共3次。24h后GM-1组静脉注射GM-1 30mg/kg,每天1次,连续7d,sham组和saline组在相应时点注射等量生理盐水。各组于给予布比卡因后(注药后)1、3、5、7、14、28d测大鼠甩尾反应潜伏期(TFL),换算成最大抗辐射热效应百分比(%MPE),并行运动功能BBB评分。每组于注药后1、3、5、7、14和28d随机处理6只大鼠,取脊髓组织,光镜、电镜下观察组织损伤评分(SD),免疫组化法和半定量逆转录-聚合酶链式反应(RT-PCR)测神经元caspase-3的表达。结果与saline组比较,GM-1组%MPE、SD及caspase-3mRNA相对表达量在注药后7、14、28d明显降低,caspase-3蛋白表达在注药后5、7、14、28d明显降低,BBB评分注药后14、28d明显提高(P<0.05);与sham组比较,GM-1组和saline组在注药后1、3、5、7、14、28d的%MPE、SD及caspase-3蛋白表达和caspase-3mRNA相对表达量明显升高,BBB评分明显降低(P<0.05)。结论 GM-1可以促进大鼠鞘内注入布比卡因脊神经毒性的感觉、运动功能恢复,保护神经元,其机制可能与caspase-3基因的下调有关。Objective To investigate the therapeutic effects of intravenous monosialo ganglio-sides（GM-1）on neurotoxicity of intrathecally administered bupivacaine in rats and its possible mecha-nism.Methods One hundred and eight adult male Sprague-Dawley rats,weighing 280-300 g,were randomly divided into 3 groups （n=36 each）：sham operation group （group sham）,group saline and group GM-1.Neurotoxicity model was performed by injecting 0.12μl/g body weight of bupivacaine at concentrations of 5% via an implanted intrathecal catheter at 90-minute intervals for 4.5 h in groups saline and GM-1.After observing 24 h,group GM-1 was administered GM-1 30 mg/kg by intrave-nous injection for 7 days,once a day;while groups saline and sham received equal volume of normal saline.The recovery of the locomotor function was evaluated with Basso,Beattie and Bresnahan （BBB）and tail-flick latency（TFL）before injection bupivacaine and days 1,3,5,7,14,28 after in-jection,TFL was converted to the percent maximum possible effect （%MPE）.Six rats were sacri-ficed in each group at each time point,and spinal cord was taken to examine histological injury scores by light and electron microscopy at the L3 level,and neuron caspase-3 expression was evluated using immunohistochemistry and RT-PCR.Results Compared with group saline,%MPE,histological inju-ry score and caspase-3 mRNA expression were decreased on days 7,14 and 28;Caspase-3 protein ex-pression was decreased on days 5,7,14 and 28;while BBB score was higher on days 14 and 28 in group GM-1 （P 〈 0.05 ）.Compared with group sham,% MPE,histological injury score,caspase-3 mRNA and protein expression in groups GM-1 and saline were significantly higher,while BBB score was lower on 1,3,5,7,14 and 28 d after injection （P 〈0.05）.Conclusion GM-1 can promote neuro-functional recovery after bupivacaine neurotoxicity in rats through the possible mechanism of down-regulating neuron caspase-3 expression.

关 键 词：布比卡因 神经毒性 神经节苷脂 大鼠 

分 类 号：R614[医药卫生—麻醉学]