CAJ | 학술논문

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。24 h 后 GM-1组静脉注射 GM-130 mg/kg,每天1次,连续7 d,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、28 d 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28 d 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-3 mRNA 相对表达量在注药后7、14、28 d 明显降低,caspase-3蛋白表达在注药后5、7、14、28 d 明显降低,BBB 评分注药后14、28 d 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、28 d 的%MPE、SD 及 caspase-3蛋白表达和 caspase-3 mRNA 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。
목적：탐토정맥주사단타액산신경절감지(GM-1)대대서초내주입포비잡인척신경독성적치료작용。방법108지웅성 SD 대서수궤균분위삼조：가수술조(sham 조)、생리염수조(saline조)화 GM-1조。saline 조화 GM-1조행초내치관,간격1.5소시중복주입5%포비잡인0.12μl/g 공3차。24 h 후 GM-1조정맥주사 GM-130 mg/kg,매천1차,련속7 d,sham 조화 saline 조재상응시점주사등량생리염수。각조우급여포비잡인후(주약후)1、3、5、7、14、28 d 측대서솔미반응잠복기(TFL),환산성최대항복사열효응백분비(%MPE),병행운동공능 BBB 평분。매조우주약후1、3、5、7、14화28 d 수궤처리6지대서,취척수조직,광경、전경하관찰조직손상평분(SD),면역조화법화반정량역전록-취합매련식반응(RT-PCR)측신경원 caspase-3적표체。결과여 saline 조비교,GM-1조%MPE、SD 급 caspase-3 mRNA 상대표체량재주약후7、14、28 d 명현강저,caspase-3단백표체재주약후5、7、14、28 d 명현강저,BBB 평분주약후14、28 d 명현제고(P <0.05)；여 sham 조비교,GM-1조화 saline 조재주약후1、3、5、7、14、28 d 적%MPE、SD 급 caspase-3단백표체화 caspase-3 mRNA 상대표체량명현승고,BBB 평분명현강저(P <0.05)。결론 GM-1가이촉진대서초내주입포비잡인척신경독성적감각、운동공능회복,보호신경원,기궤제가능여 caspase-3기인적하조유관。
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.