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

该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3 d或7 d 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4 d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 Effects of Environmental Enrichment on Neuron Apoptosis and Expression of XIAP Following Cerebral Ischemia and Rreperfusion in Mice

The aim of the present study is to investigate whether the effects of environmental enrichment on learning-memory deficits are associated with inhibition of apoptotic cell death and up-regulation of XIAP mRNA expression following cerebral ischemia and reperfusion in mice. The adult male ICR mice were established the cerebral ischemia-reperfusion model by repeated fastening bilateral common carotid artery. Control mice received sham surgery, in which the bilateral common carotid artery did not fastened. One day after surgery, the ischemic and sham mice were randomly assigned for enriched environment housing or standard environment housing for 3 or 7 days, and then submitted to spontaneous behavioral testing in open field and learning-memory performance in Morris water maze. DNA damage induced by cerebral ischemia was detected by agarose gel electrophoresis techniques, and the expression of XIAP mRNA was checked by RT-PCR. The Results showed that environmental enrichment after cerebral ischemia significantly improved the learning-memory damage induced by cerebral ischemia. After 4 days of repeat ischemia-reperfusion, obvious DNA ladder and decreased neuron density were observed in hippocampus CA1 of ischemic mice, but disappeared by environmental enrichment. In correspondence with these results, the down-regulated expression of XIAP mRNA in hippocampus of ischemic mice was inhibited by enriched environment housing for 7 days. The findings suggest that up-regulation of XIAP mRNA expression and inhibition of neuron apoptosis maybe associated with the improvement of spatial learning-memory in cerebral ischemic mice after environmental enrichment.