缺血预处理后Fas蛋白表达与迟发性神经元凋亡的关系初步探讨  

Preliminary study of the relationship between Fas protein expression and delayed neuronal apoptosis induced by global cerebral ischemia after ischemic preconditioning

作　　者：邓志锋[1] 李明[1] 汪泱[2] 宋书欣[1] 

机构地区：[1]江西医学院第二附属医院神经外科,江西医学院脑血管研究所,330006 [2]江西医学院泌尿外科研究所

出　　处：《中华神经外科杂志》2004年第6期471-475,共5页Chinese Journal of Neurosurgery

基　　金：江西省自然科学基金资助项目(0040037)

摘　　要：目的动态观察缺血预处理后大鼠大脑皮层和海马CA1区神经元凋亡与Fas蛋白表达变化情况,初步探讨缺血预处理后Fas蛋白表达与迟发性神经元凋亡的关系。方法四血管阻断法复制全脑缺血模型,动物随机分为非缺血对照组、预处理对照组、缺血预处理组和缺血组。采用尼氏和TUNEL染色法观察皮层及海马CA1区神经元存活数和凋亡细胞数,免疫组化方法检测Fas蛋白在缺血预处理后表达变化情况。结果缺血组缺血6h在皮质及海马CA1区Fas阳性表达细胞计数升高,12h达高峰;缺血预处理组缺血12h阳性细胞计数升高,24h达高峰。缺血组缺血6h出现凋亡细胞,48h凋亡细胞数达到高峰;缺血预处理组凋亡细胞数较缺血组明显减少。缺血组缺血7d神经元数明显减少,12周时神经元大量减少;缺血预处理组缺血7d时神经元数无明显变化,但12周时神经元同样大量减少。结论全脑缺血可能通过诱导Fas蛋白的表达增多,启动细胞凋亡,导致缺血后神经元凋亡的发生;缺血预处理虽可延缓缺血后神经元的凋亡,但无法提供真正的长时期的神经元保护作用,其有限的保护作用可能是通过延缓Fas蛋白的表达而减缓了神经元凋亡的进程。Objective Danamically observe the effects of ischemic preconditioning on Fas protein expression and delayedneuronal apoptosis induced by global cerebral ischemia in the cortex and hippocampal CA1 region of rat in order to investigate the relationship between Fas protein expression and delayed neuronal apoptosis after ischemic preconditioning. Methods Global cerebral ischemia was induced in rats by four-vessel occlusion. Animals were allocated to the following groups before the experiment: sham (S); preconditioned only (PO); ischemic preconditioned(IP); and ischemia(I). Nissl staining and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) were used to count the numbers of alive neuron and apoptosis in the cortex and hippocampal CA1 of rats. Immunohistochemistry with Fas protein polyclonal antibody was used to explore the varieties of Fas protein expressions after global cerebral ischemia. Results The Fas -expressing cells of I animals began to increase at 6 hours after global cerebral ischemia, arrived peak at 12 hour; those of IP animals began to increase at 12 hours and arrived peak at 24 hours after global cerebral ischemia. In I animals there were a few apoptosis at 6 hours, then the quantity of apoptosis arrived peak at 48 hours after global cerebral ischemia, the apoptotic cells of IP animals at various moment were less significantly than those of I animals. The alive neurons of cortex and hippocampus reduced remarkably at 7 days and there were few alive neurons at 12 weeks after global cerebral ischemia in I animals. After 7 days of global cerebral ischemia, the number of alive neurons of IP animals showed no significant changes, but there were few alive neurons at 12 weeks. Conclusions Global cerebral ischemia can result in neurons apoptosis by inducing Fas expression. Ischemic preconditioning can delay apoptosis induced by ischemia, but it can not provide substantial and long-termneuroprotection. The neuroprotection attained by ischemic preconditioning may only delay the

关 键 词：缺血预处理 FAS蛋白 神经元凋亡 表达 凋亡细胞 迟发性 海马CA1区 高峰 结论 时期 

分 类 号：R741[医药卫生—神经病学与精神病学]