新生鼠脑缺血预处理后海马CA1区GAP-43的表达

目的:观察新生Wistar鼠脑缺血再灌注后海马CA1区生长相关蛋白43(GAP-43)的表达和意义. 方法:通过阻断7日龄新生Wistar大鼠右侧颈总动脉45 min制备脑缺血模型,设置假手术组、缺血再灌注组和预缺血-缺血再灌注组. 采用免疫组化方法和计算机图像分析技术检测三组新生鼠不同时点海马CA1区脑组织GAP-43的动态变化及三组光镜下脑组织病理改变. 结果: ①脑组织病理改变:假手术组大鼠无异常病理改变,缺血再灌注组神经细胞变性、坏死,预缺血组-病理损伤较缺血再灌注组轻. ②GAP-43表达:缺血再灌注组海马GAP-43表达在再灌注后24 h时开始增高,7 d达高峰,至14 d与假手术组比较差异有统计学意义(P＜0.05);预缺血-缺血再灌注组GAP-43表达较缺血再灌注组增加更明显,与假手术组和缺血再灌注组比较均差异有统计学意义(P＜0.05). 结论: 新生鼠脑缺血预处理可减轻再次严重脑缺血对神经细胞的损伤,脑缺血预处理后海马CA1区GAP-43表达和合成增加,GAP-43表达增加可能与神经元再生和轴突重塑有关,是脑缺血后神经细胞内源性代偿机制之一.

Expression and significance of GAP-43 in hippocampal CA1 region after cerebral ischemic preconditioning in neonatal rats

AIM: To investigate the expression and significance of growth-associated protein-43 (GAP-43) in hippocampal CA1 region of 7-day-old Wistar rats with cerebral ischemic preconditioning. METHODS: Cerebral ischemia in 7-day-old Wistar rats was induced by occluding right common carotid artery for 45 min. The Wistar rats were randomly divided into sham-operation group (A), ischemia-reperfusion group (B) and ischemic preconditioning group (C). In group C transient cerebral ischemia for 8 min was preformed before the serious cerebral ischemia (for 45 min) after 24 h interval. The pathological changes in the brain were observed by optical microscope, and immunohistochemistry and computer image analysis system were used to detect the expression of GAP-43. RESULTS: No brain damage was found in group A, the neurocytes were degenerative and necrotic in group B. The pathological manifestations of the brain damage in group C were milder than those in the group B. The expression of GAP-43 in hippocampal CA1 region in group B markedly increased at 24 h after reperfusion, reached peak at 7 d, and keep in a high level to 14 d after reperfusion (P<0.05 vs group A). The expression of GAP-43 in hippocampal CA1 region of group C was higher compared with the group B and A; there were significant differences from 24 h to 14 d (P<0.05 vs group A and B). CONCLUSION: The cerebral ischemic preconditioning can relieve the brain damage due to a subsequent more severe ischemia in neonatal rats. The expression of GAP-43 markedly increased in hippocampal CA1 region in ischemic preconditioning group, which may be involved in the axonal plasticity and regeneration of neurocytes, one of the endogenous compensatory mechanisms of neuron after cerebral ischemia.