鞘内注射单唾液酸神经节苷脂对布比卡因椎管麻醉诱发大鼠脊髓毒性的治疗效果  

Efficacy of intrathecally administered monosialoganglioside for treatment of bupivacaine spinal anesthesia-induced neurotoxicity to rat spinal cord

作　　者：吉杰梅[1] 陆华良[1] 谷万杰[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,南宁市530021

出　　处：《中华麻醉学杂志》2013年第7期815-818,共4页Chinese Journal of Anesthesiology

摘　　要：目的 评价鞘内注射单唾液酸神经节苷脂（GM-1）对布比卡因椎管麻醉诱发大鼠脊髓毒性的治疗效果.方法 健康成年雄性SD大鼠,体重280～300 g,于L3,4椎间隙向尾端行鞘内置管,取鞘内置管成功的大鼠144只,采用随机数字表法,将其分为4组（n=36）：假手术组（S组）、GM-1组、布比卡因组（B组）和布比卡因＋ GM-1组（BG组）.B组和BG组鞘内注入5％布比卡因20μl,间隔1.5h给药1次,共3次,24 h后,BG组和GM-1组鞘内注射GM-1 20 μg,1次/d,连续7d.于鞘内注射布比卡因前及注射后1、3、5、7、14、28 d（T0-6）时测定甩尾反应潜伏期（TFL）,计算最大抗辐射热效应（MPE）百分比,并行后肢运动功能评分（BBB评分）；TFL和BBB评分测定后取脊髓组织,行HE染色,观察组织病理学改变,光镜和电镜下行组织损伤评分；采用免疫组化和RT-PCR法测定脊髓caspase-3蛋白及其mRNA表达水平.结果 与S组和GM-1组比较,B组T1-6时MPE百分比、组织损伤评分、脊髓caspase-3 mRNA和蛋白表达水平升高,BBB评分降低（P＜0.05）,BG组T1-5时MPE百分比升高（P＜0.05）,T6时恢复至基础值（P＞0.05）,T1-6时BBB评分降低,脊髓组织损伤评分、caspase-3 mRNA和蛋白表达水平升高（P＜0.05）.S组和GM-1组各时点各指标比较差异无统计学意义（P＞0.05）.与B组比较,BG组T2-6时MPE百分比、脊髓caspase-3 mRNA及蛋白表达水平降低,T3-6时脊髓组织损伤评分降低,T4-6时BBB评分升高（P＜0.05）.B组T1-6时脊髓组织病理学损伤明显,BG组T1-3时脊髓组织病理学损伤明显,T4-6时逐渐恢复.结论 鞘内注射GM-1对布比卡因椎管麻醉诱发大鼠脊髓毒性有治疗效果,其机制与抑制脊髓神经细胞凋亡有关.Objective To evaluate the efficacy of intrathecally administered monosialoganglioside （GM-1）for treatment of bupivacaine spinal anesthesia-induced neurotoxicity to rat spinal cord.Methods Adult male Sprague-Dawley rats,weighing 280-300 g,in which the intrathecal catheter was successfully inserted into the L3,4 intervertebral space and advanced toward the tail,were randomly divided into 4 groups （n =36 each）：sham operation group （group S）,GM-1 group,bupivacaine group （group B） and bupivacaine ＋ GM-1 group （group BG）.In B and BG groups,the rats received 5％ bupivacaine 20 μl via the intrathecal catheter 3 times at 1.5-hour intervals.GM-1 20 μg was injected intrathecally 24 h later once a day for 7 days in BG and GM-1 groups.Before bupivacaine injection and on days 1,3,5,7,14 and 28 after bupivacaine injection （T0-T6）,tail flick latency （TFL） was measured,MPE （percentage of maximal possible effect） was calculated,and the locomotor recovery was evaluated using the Basso,Beattie,Bresnahan （BBB） Locomotor Rating Scale.Then six rats were randomly chosen and sacrificed in each group.Spinal cord was removed for histopathologic examination （with light and electronic microscope） and for determination of caspase-3 protein and mRNA expression （by immuno-histochemistry and RTPCR）.The pathological changes of the spinal cord were scored.Results Compared with S and GM-1 groups,MPE,pathological scores,and caspase-3 protein and mRNA expression were significantly increased and BBB score was decreased at T1-6 in group B （P ＜ 0.05）,and MPE was increased at T1-5 （P ＜ 0.05） and returned to the baseline value at T6 （P ＞ 0.05） and pathological scores,and caspase-3 protein and mRNA expression were significantly increased and BBB score was decreased at T1-6 in group BG （P ＜ 0.05）.There were no significant differences in each parameter at each time point between S and GM-1 groups （P ＞ 0.05）.Compared with group B,MPE and caspase-3 protein and mRNA expression were

关 键 词：G（M1）神经节苷脂 布比卡因 神经毒性 注射 脊髓 

分 类 号：R614[医药卫生—麻醉学]