拉莫三嗪在小鼠脊髓背侧半横断损伤修复中的作用  

Role of lamotrigine in repair of hemisection of spinal cord in mice models

作　　者：付强 王兆涛 张茂营[2] 徐如祥[2] 

机构地区：[1]解放军医学院,北京100853 [2]北京军区总医院附属八一脑科医院,北京100700

出　　处：《中华神经医学杂志》2015年第8期789-793,共5页Chinese Journal of Neuromedicine

基　　金：军队十二五重大科技项目（BWS12J010）

摘　　要：目的探讨拉莫三嗪对脊髓背侧半横断损伤模型小鼠的修复作用。方法雌性C57BL／6小鼠80只中成功制作脊髓背侧半横断损伤模型小鼠79只，并按随机数字表法分为模型组（n=27）、治疗组（n=261、对照组（n=26）。模型组小鼠在脊髓损伤后不予其他处理；治疗组小鼠术后1d腹腔注射拉莫三嗪（25mg／kg），连续7d；对照组小鼠注射等量生理盐水。术后1d、7d、14d对各组小鼠行BBB评分；并在1d、7d、14d每组取6只小鼠处死，取出损伤的脊髓并制作冰冻切片，免疫荧光染色检测神经胶质纤维酸性蛋白（GFAP）、离子钙接头蛋白1（1ba1）阳性细胞；术后7d每组取6只小鼠，ELISA检测损伤脊髓白介素（IL）-1、IL-10、肿瘤坏死因子-α（TNF-α）的水平。结果术后7d、14d治疗组小鼠的BBB评分（5．1667±0．4083、6．5000±0．5477）高于模型组（4．0000±0．6325、5．5000±0．5477）和对照组（3．8333±0．4083、5．3333±0．5164）；GFAP^＋细胞免疫荧光面积百分比、每mm^2的Ibal^＋细胞数量低于模型组和对照组，差异均有统计学意义（P〈0．05）；术后7d治疗组小鼠损伤脊髓中IL．1和IL．10表达水平低于模型组和对照组，差异有统计学意义（P〈0．05）。结论拉莫三嗪可以改善脊髓损伤小鼠的运动功能，可能是通过减少损伤脊髓炎症因子的分泌、降低胶质细胞的活化来实现的。Objective To investigate the effect oflamotrigine （LTG） on repair ofhemisection of spinal cord in mice models. Methods A total of 80 female C57BL/6 mice were employed to establish the models of spinal cord hemisection, and randomly divided into 3 groups： spinal cord injury （SCI） group （n=27）, SCI＋LTG group （n=26） and SCI＋0.9% saline group （n=26）; mice in SCI＋LTG group were given intrape/itoneal injection of lamotrigine （25 mg/kg） for a consecutive 7 d, and mice in the SCI＋0.9% saline group were given the same volume of 0.9% saline. Basso, Beatti, Bresnahan （BBB） scale was performed 1, 7 and 14 d after SCI; 6 mice in each group were sacrificed 1, 7 and 14 d after SCI, and glial fiber acidic protein （GFAP） and ionized calcium-binding adaptor molecule 1 （Ibal）-positive cells were observed by immunofluorescence and the expressions of inflammatory factors interleukin （IL）-1, IL-10 and tumor necrosis factor （TNF-α） were observed by ELISA. Results On the 7^th and 14^th d of injury, the BBB scale scores in the SCI＋LTG group were significantly higher than those in the SCI group and SCI＋0.9% saline group （7 d： 5.1667±0.40825, 4.0000±0.63246 and 3.8333±0.40825; 14 d： 6.5000± 0.5477, 5.5000±0.5477 and 5.3333±0.5164, P〈0.05）. On the 7^th and i4^th d of injury, less percentage of GFAP positive fluorenscent area and fewer number of Ibal positive cells in the SCI＋LTG group were noted than those in the SCI group and SCI＋0.9% saline group （P〈0.05）. On the 7^th d of SCI, the IL-1 and IL-10 expressions in the SCI＋LTG group were obviously lower than those in the SCI group and SCI＋ 0.9% saline group （P〈0.05）. Conclusion Lamotrigine improves the motor fi.mction after SCI bydecreasing the secretion of inflammatory factors and activation of glial cells.

关 键 词：脊髓损伤 拉莫三嗪 胶质细胞 炎症因子 

分 类 号：R651.2[医药卫生—外科学]