大鼠局灶性脑缺血再灌注损伤后GAP-43及IGF-1促进神经元再生表达的实验研究

Experiment promotion nerons regeneration and expression of GAP-43 proteins and IGF-1 proteins after focal cerebral ischemia reperfusion injury in rats

目的探讨Wistar大鼠脑缺血再灌注损伤后生长相关蛋白GAP-43抑制神经元凋亡和胰岛素样生长因子-I（IGF-1），促进神经元再生的可塑性表达机制。方法将80只成年健康雄性Wistar大鼠，分为GAP-43组和IGF-1组，每组各40只，并随机分为正常对照组、假手术组和缺血1h再灌注2h、6h、12h、24h、48h、3d、7d、14d组，每组4只（n=4）。应用线栓法制备大鼠脑缺血再灌注动物模型，并采用免疫组织化学方法检测GAP-43与IGF-1在神经元凋亡中的表达情况，并进行图像分析。结果GAP-43组：缺血再灌注2h，海马、皮质区及纹状体区神经元GAP-43呈基础表达，6-48h表达逐渐增高，7d达高峰，14d达最低，P〈0.05。与假手术组比较有显著性差异，P〈0.05。IGF-1组：正常对照组及假手术组在海马区、皮质区及纹状体区IGF-1阳性标记出芽细胞呈基础表达。缺血再灌2h IGF-1表达明显增高，24h达高峰，P〈0.05。48h恒定表达。3-14d仍维持高值表达，P〈0.05。结论GAP-43与IGF-1参与抑制并促进神经元轴突再生的表达。

Objective To explore of the the mechanism of the expression of GAP-43 proteins inhibition neu-rons apoptosis and IGF-1 proteins promotion neurons regeneration after cerebral ischemia reperfusion injury in Wistar rats. Methods The healthy adult of male Wister rats （80） were divided into GAP-43 group and IGF-1 group,per group （40）,and they divided andomly into normal control group and sham-operation group and in ischemic lh reperfusion 2h, 6h, 12h, 24h, 48h, 3d, 7d, 14d group （n = 4）. The models with cerebral ischemic reperfusion were induced by intraluminal middle cerebral artery occlusion （MCAO） with a nylon monofilament suture. And using immunohistochemistry technique detecte the condition of the expression of GAP-43 proteins and IGF-1 proteins in apoptosis of neurons,and by a computer image analysis system. Results GAP-43 group：Showing the expression of background of GAP-43 of neurons in hippocampus and cortical area and striatal area in cerebral ischemia reperfusion in 2h ,The expression of GAP-43 showed gradually increase in 6h, 12h, 24h, 48h, the expression of it reached peak in 7d,the expression of it reached lowest the level in 14d,P〈0.05. It compare with sham-opera- tion is significancely difference,P〈0.05. IGF-1 group：Showing the expression of background of positive GAP-43 of budding cells in hippocampus and cortical area and striatal area on normal control group and sham-operation group. The expression of IGF-1 is clearly increase in ischemic reperfusion in 2h ,and reached peak in 24h ,P〈0.05, and expressed constant in 48h. It still keeped high the expression from 3d to 14d,P〈0.05. Conclusion The expression of C, AP-43 and IGF-1 participate in the inhibition and promotion of neuron axon regeneration.