GCSF对亚急性脑缺血老龄鼠认知障碍及海马损伤的修复作用

目的 探讨GCSF对亚急性脑缺血老龄鼠认知障碍及神经损伤的修复作用，并分析行为学认知改善与组织学病理变化的相关性。方法 14月龄雄性SD大鼠2VO术后饲养1个月，构建2VO亚急性脑缺血老龄鼠模型。随机分组，建模后存活大鼠2VO/NS组7只，Sham/NS组8只、2VO/GCSF组7只。Morris水迷宫实验评估大鼠学习记忆功能，免疫组化及荧光染色后对海马CA1区锥体细胞、凋亡细胞计数分析。结果 行为学认知功能评估：2VO/NS组大鼠逃逸潜伏期长于Sham/NS组（P＜0.01）和2VO/GCSF组（P＜0.05）；2VO/NS组大鼠停留于平台所在象限的时间少于Sham/NS（P＜0.01）和2VO/GCSF组（P＜0.05）；2VO/NS组大鼠跨越平台区域的次数少于Sham/NS（P＜0.01）和2VO/GCSF组（P＜0.01）。组织学图像分析：海马CA1区NeuN阳性细胞2VO/NS组少于Sham/NS组（P＜0.01）和2VO/GCSF组（P＜0.01）；凋亡细胞2VO/NS组多于Sham/NS组（P＜0.01）和2VO/GCSF组（P＜0.05）。认知改善与组织学变化的相关性：2VO/NS组、Sham/NS及2VO/GCSF组海马CA1区NeuN阳性细胞、凋亡细胞的数量变化分别与记忆功能呈正相关、负相关。结论 GCSF可有效改善亚急性脑缺血所致的学习记忆认知障碍。其中，促海马锥体细胞增生、抑制凋亡，是GCSF改善认知障碍的重要修复机制。

GCSF induced repair of cognitive handicap and hippocampus injury in senile rats with subacute cerebral ischemia

【Abstract】 Objective To approach the protective effects of GCSF treating hippocampus injury and cognitive handicap, analyze their correlation after subacute cerebral hypoperfusion in aged rats. Methods 14 months male SD rats were regular rear for 1 month after bilateral common carotid arteries occlusion surgery(2VO). The survival rats were randomly divided into 2VO/NS (n=7), Sham/NS (n=8) and 2VO/GCSF (n=7) group. Spatial learning and memory was accessed by Morris Water Maze, immunohistochemistry and immunofluorescence were employed to detected the number of neuron hyperplasia and apoptosis in hippocampal CA1 region. Results Functional assessment: Escape latency of 2VO/NS group was longer than Sham/NS (P<0.01)and 2VO/GCSF group (P<0.05). 2VO/NS group rats spent less time in the platform quadrant than Sham/NS (P<0.01)and 2VO/GCSF group (P<0.05). Times of 2VO/NS group crossing the platform area was less than Sham/NS (P＜0.01) and 2VO/GCSF group (P＜0.01). Image analysis: NeuN positive cells of 2VO/NS group were less than Sham/NS(P<0.01) and 2VO/GCSF group(P<0.01) in hippocampal CA1 region. Apoptosis cells of 2VO/NS group were more than Sham/NS(P<0.01) and 2VO/GCSF group (P<0.05). Number of NeuN positive cells was positive related to spatial memory among 2VO/NS, Sham/NS and 2VO/GCSF group, number of apoptosis cells was negative related to spatial memory. Conclusion GCSF can improve cognitive handicap which subacute cerebral hypoperfusion caused in aged rats. GCSF can promote pyramidal cell hyperplasia and inhibite cell apoptosis, this is important pathological mechanism of cognition improvement.