摘要
目的 探讨经尾静脉注射新型钾离子通道阻滞剂4-氨基吡啶-3-甲醇（4-aminopyridine-3-methanol,4-AP-3-MeOH）对大鼠慢性脊髓损伤的治疗作用.方法 选取18只成年健康雄性SD大鼠,随机分为3组：4-AP-3-MeOH治疗组、生理盐水对照组和假手术组.对4-AP-3-MeOH组和生理盐水组大鼠均行脊髓T10节段水平压迫损伤,28 d后每日对4-AP-3-MeOH组进行尾静脉注射4-AP-3-MeOH 1 μmol,连续注射4周;生理盐水组同期注射等量生理盐水.对假手术组大鼠仅行T10椎板切除,不压迫脊髓.所有大鼠术后行Basso Beattie Bresnahan （BBB）评分和斜板试验评价行为运动功能,同时行体感诱发电位（somatosensory evoked potential,SEP）和运动诱发电位（motor evoked potential,MEP）检测.结果 术后4周,4-AP-3-MeOH组和生理盐水组在行为学（BBB评分和斜板试验）和神经电生理检测结果差异上均无统计学意义.4-AP-3-MeOH组从第6周开始BBB评分逐渐增加并高于生理盐水组,差异有统计学意义,但两组各时间点BBB评分均小于假手术组,差异均有统计学意义.4-AP-3-MeOH组与生理盐水组的斜板角度从术后第1天到8周的差异均无统计学意义,且均小于假手术组,差异均有统计学意义.神经电生理检测发现从第4周到第8周4-AP-3-MeOH组的SEP和MEP波幅值均高于生理盐水组,差异有统计学意义,但低于假手术组.组织学染色：假手术组大鼠脊髓形态完整,灰白质分界清晰;4-AP-3-MeOH组和生理盐水组大鼠脊髓可见灰质结构消失,脊髓中央可见大的空腔,白质周边可见脱髓鞘病变.同时4-AP-3-MeOH组大鼠脊髓损伤中心处的残存髓鞘百分比高于生理盐水组（0.56±0.06 vs 0.42±0.05）.结论 大鼠慢性脊髓损伤时,于尾静脉长期连续注射4-AP-3-MeOH可以在一定程度上促进脊髓的神经传导功能恢复,改善大鼠的感觉和运动功能.
Objective To investigate the therapeutic effect of the new K＋ channel blocker 4-aminopyridine-3-methanol （4-AP-3-MeOH） on chronic spinal cord injury in rats.Methods 18 adult male Sprague-Dawley rats were randomly divided equally into 3 groups as follows：4-AP-3-MeOH treatment group （A）,normal saline control group （B） and sham operation group （C）.T10 segment of spinal cord compression injury was applied in group A and group B.4 weeks later,the rats in group A were daily treated by injecting 4-AP-3-MeOH 1 μmol （1000 μmol/L＆#215; 1 ml） into the veins of the tails for 4 weeks.While the same volume of saline was administrated into the group B for 4 weeks.Lamina of vertebra of T10 was cut without spinal cord injury in the sham-operation group.After modeling,the locomotor functional recovery was assessed by using Basso Beattie Bresnahan （BBB） scores and inclined plane （IP） tests,and all rats were periodical inspected by the somatosensory evoked potential（SEP） and motor evoked potential（MEP） post-operatively.Results BBB scores of group A started to increase gradually and were higher than those of group B from the 6th week,but the 2 groups at each time point in BBB scores were less than group C.Until 8 weeks after surgery,the inclined-plated angles of group A and B did not show significantly difference,but the both groups were significantly lower compared with group C.Electrophysiology study found that the amplitude of SEP and MEP in group A was higher than group B from the fourth to 8 weeks,but less than in group C.Histological examination showed that the spinal cord of rats in group C were morphologically intact with a clear demarcation between the grey and white matter.The gray matter structures of rats in group A and B were gone and a big cavity appears in the center of the spinal cord injury,with varying degrees of demyelination in the white around.In addition,statistically significant differences were found in the percentage of residual myelin at the injury epicenter betwee
出处
《中华骨科杂志》
CAS
CSCD
北大核心
2016年第10期626-633,共8页
Chinese Journal of Orthopaedics
基金
E海市卫汁委重茛陴研基金（20114018）
上海市卫计委优秀学科带头^培养项目（新百人计划,（XBR2011024）
关键词
脊髓损伤
脱髓鞘疾病
组织学
比较
Spinal cord injuries
Demyelinating diseases
Histology,comparative
