粒细胞集落刺激因子结合行为训练对缺血性脑损伤大鼠早期干预的研究

Early Intervention of Granulocyte Colony Stimulating Factor Combined with Behavior Training for Ischemic Brain Injury in Rats

目的探讨粒细胞集落刺激因子(G-CSF)结合行为训练对缺血性脑损伤大鼠的神经保护作用及对远期学习记忆能力的影响。方法 2月龄清洁级Wistar大鼠96只,分为假手术组(A组)、模型组(B组),G-CSF干预组(C组)及G-CSF+行为训练组(D组)。采用改良线栓法制作大鼠大脑中动脉闭塞(MCAO)2 h再灌注24 h模型(A组不插入线栓)。各组分别于造模成功后1周、2周、4周、8周随机选取6只,利用穿梭实验视频分析系统计算逃避潜伏总时间,HE染色和免疫组织化学染色观察造模后大鼠海马区病理变化及神经生长因子(NGF)、G-CSF水平。结果造模后,B组NGF、G-CSF表达短暂升高,C、D组表达总体上高于B组,尤以D组为著(P<0.05);逃避潜伏总时间各组均延长,总体上B组长于C组,C组长于D组(P<0.05)。随着时间的延长,这一趋势更加明显。结论结合行为训练较单一应用G-CSF神经保护作用更强,且显著提高远期学习记忆能力。

Objective To investigate the neuroprotective effect of granulocyte colony stimulating factor （G-CSF） combined with behav- ior training on the learning and memory abilities of cerebral ischemic injury in rats. Methods 96 Wistar rats, 2 months old, were divided as sham group （group A）, model group （group B）, G-CSF group （group C） and G-CSF＋training group （group D）. Modified middle cerebral ar- tery occlusion （MCAO） was used to establish a ischemia 2 h/reperfusion 24 h model to all the rats, except sham group. 6 rats were selected in each group 1, 2, 4 and 8 weeks after successfully modeled, respectively. The abilities of learning and memory were detected with the la- tency of shuttle test video analysis system. The pathology of the hippocampus and the expression of nerve growth factor （NGF） and G-CSF were observed with HE and immunohistochemistry staining, respectively. Results The expression of NGF and G-CSF increased in group B transiently, and increased more and longer in the group C and D, especially in group D, as the time passed （P〈0.05）. The latency of shuttle test increased in group B, C and D, and gently decreased as the time passed, and the decrease more to less were group D, C and B （P〈0.05）. Cunelusion The neuroprotective effects of G-CSF combined with behavior training are strengthened and long term beneficial than G-CSF alone.