丰富环境对脑缺血再灌注小鼠神经细胞凋亡和XIAP基因表达的影响

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本研究主要探讨丰富环境干预对脑缺血再灌注小鼠神经细胞凋亡的影响。实验采用健康雄性ICR小鼠,随机分为丰富环境缺血组(IE)、标准环境缺血组(IS),同时分别设丰富环境假手术组(SE)、标准环境假手术组(SS)。通过双侧颈动脉重复结扎建立小鼠全脑缺血再灌注模型,分别在缺血后在丰富环境和标准环境饲养3d或7d后,进行开场行为和水迷宫空间记忆行为检测;同时进行神经细胞损伤的组织学观测,并采用琼脂糖凝胶电泳技术分析DNA片段化,用RT-PCR检测X染色体连锁的凋亡抑制蛋白(X-linked inhibitor of apoptosis protein,XIAP)mRNA的表达。结果表明,丰富环境干预能有效改善脑缺血导致的自发活动、探究行为减少和空间学习记忆能力减退,并对正常小鼠也有促进作用。缺血再灌注4d的海马神经细胞损伤较严重,神经元密度显著减少,脑组织DNA片段化明显增强,丰富环境作用使神经细胞损伤和DNA片段化程度均有所减轻。同时丰富环境作用可抑制反复脑缺血再灌注导致的XIAP mRNA表达下调。可见,丰富环境干预可改善脑缺血小鼠的自发活动、探究行为和空间学习记忆能力,该作用可能与其抑制神经细胞XIAP基因表达下调、减弱脑缺血再灌注诱导的神经细胞凋亡有关。 The aim of this study was to investigate the effect of environmental intervention on neuronal apoptosis in mice with cerebral ischemia / reperfusion. Healthy male ICR mice were randomly divided into three groups: the intensive environmental ischemic group (IE) and the standard environmental ischemic group (IS). At the same time, we established the rich environmental sham operation group (SE) and the standard environmental sham operation group (SS) respectively. The model of global cerebral ischemia / reperfusion in mice was established by repeated ligation of bilateral carotid arteries. The opening behavior and spatial memory behavior of water maze were detected after 3 days or 7 days of ischemia respectively in the environment and standard environment. At the same time, Histological observation was performed. DNA fragmentation was analyzed by agarose gel electrophoresis. The expression of X-linked inhibitor of apoptosis protein (XIAP) mRNA was detected by RT-PCR. The results showed that abundant environmental intervention can effectively improve the spontaneous activity induced by cerebral ischemia, explore the reduction of behavior and spatial learning and memory abilities, and also promote normal mice. The hippocampal neurons injured more severely 4 days after ischemia-reperfusion, the density of neurons decreased significantly, and the DNA fragmentation of brain tissue increased obviously. Enrichment of the environment reduced the damage of nerve cells and the degree of DNA fragmentation. At the same time, it can inhibit the down-regulation of XIAP mRNA expression induced by repeated cerebral ischemia and reperfusion. It can be seen that abundant environmental intervention can improve spontaneous activity of mice with cerebral ischemia and explore behavioral and spatial learning and memory abilities, which may be related to the inhibition of XIAP gene expression in nerve cells and the decrease of apoptosis induced by cerebral ischemia-reperfusion.
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