摘要
目的:探讨大鼠脑缺血再灌注损伤后激发内源性GAP-43和Bcl-2促进凋亡神经元可塑性再生并介导海马缺血半影区代偿性修复的作用。方法:成年健康雄性Wistar大鼠100只,随机分为正常组和假手术组各10只,再灌注组80只。再灌注组应用线栓法制备大鼠脑缺血再灌注模型,根据缺血再灌注时间细分为再灌注2、6、12、24、48h及3、7和14d8个时间点各10只,缺血时间均为1h,采用免疫组织化学方法检测TUNEL、GAP-43和Bcl-2在神经元中的表达,用TTC法观察海马梗死灶的改变。结果:正常组和假手术组大鼠脑组织偶见TUNEL阳性细胞。再灌注组与前2组比较,缺血再灌注2h点TUNEL阳性细胞增加,48h达高峰,14d时降至最低;神经元GAP-43缺血再灌注2h点呈基础表达,3～7d达高峰,14d时降至最低;神经元Bcl-2表达缺血再灌注2h点增加,7d达高峰,14d降至最低;梗死灶于再灌注2h点开始逐渐形成,48h点梗死面积最大,以后梗死面积逐渐减少,至14d时恢复正常水平。结论:脑缺血后激发内源性GAP-43和Bcl-2表达可能促进神经元轴突再生;神经元凋亡可能参与内源性相关凋亡基因激活途径。
Objective： To explore the effect of activated endogenous growth associated protein-43 （GAP-43） and Bcl-2 promoting plasticity regeneration of apoptotic neurons and mediating a compensated repair of isehemic penumbral region in hippocampus after cerebral ischemia reperfusion injury in rats. Methods.. The healthy adult male Wister rats （n= 100） were randomly divided into normal control group, sham-operation group and reperfusion 2.6,12.24 and 48 h, 3.7 and 14 days after isehemia 1 h groups （n= 10 in each group）. The models of cerebral ischemia reperfusion were induced by intraluminal middle cerebral artery occlusion （MCAO） with a nylon monofilament suture. The expression of GAP-43 and Bcl-2 proteins was detected by immunohistochemistry method, and apoptosis of neurons was tested by TUNEL. Infarction size was observed by TTC staining. Results： The apoptotic neurons were increased in ischemia/reperfusion 2 h, reached the peak at 48 h, and reduced to the lowest level at 14 day. GAP-43 in neurons showed a basic expression background in ischemia/reperfusion 2 h, peaked at 3--7 day, and reduced to the lowest at 14 day. The expression of Bcl-2 was increased in ischemia/perfusion 2 h, reached the peak at 7 day, and reduced to the lowest at 14 day. Infarction size began to form in ischemia/reperfusion 2 h, reached the peak at 48 h, then gradually reduced, and returned to the normal level at 14 day. Conclusion： The expression of endogenous GAP-43 and Bcl-2 could stimulate neurons axon regeneration and synaptic linkage formation after ischemia injury. Neuron apoptosis might participate in the activation channel of endogenous correlated apoptosis genes.
出处
《中国康复》
2008年第6期371-373,共3页
Chinese Journal of Rehabilitation
基金
青岛市科技局基金资助项目(05-1-NS-73)
关键词
脑缺血再灌注损伤
缺血半影区
神经元轴突再生
GAP-43
BCL-2
细胞凋亡
cerebral ischemia/reperfusion injury
infarct penumbral region
neuron axon regeneration
growth associated protein- 43
Bcl-2
apoptosis
