间歇低氧诱导海马神经细胞凋亡和自噬曾多

摘要

Objective To investigated the effects of intermittent hypoxia on neuronal apoptosis and autophagy in hippocampus.Methods 30 Wistar rats were randomly divided into normal control group (NC),intermittent normoxia group (IN) and intermittent hypoxia group (IH).The spatial learning and memory function of the rat was assessed using Morris water maze test.The apoptotic cells and the ultrastructure of neurons in the hippocampus tissue were observed by TUNEL and transmission electron microscope,respectively.And the expression of autophagy marker protein LC3 and Beclin-1 were measured by Western blotting.Results The escape latency was significantly longer in IH than in NC and IN group.And the ratio of time spent in the target quadrant was lower in the IH group than in NC and IN group (P＜0.05).The apoptotic rate of rat hippocampal neurons (F =6.01,P=0.037),the amount of double-layer membrane structure-complicating autophagic vacuoles with karyopyknosis,and protein expression level of LC3 and Beclin-1 were significantly higher (all P ＜0.05) in intermittent hypoxia group than in IN and NC group.Conclusions Intermittent hypoxiainduced autophagy and apoptosis in rat hippocampus are significantly increased,which might be one of the possible mechanisms for cognitive dysfunction caused by intermittent hypoxia.%目的 探讨间歇低氧对大鼠海马神经细胞凋亡和自噬的影响. 方法 选取30只Wistar大鼠随机分为正常对照组(NC)、间歇常氧组(IN)和间歇低氧组(IH),采用Morris水迷宫的方法测定大鼠空间学习记忆功能的变化,TUNEL检测海马神经细胞的凋亡,透射电镜观察超微结构,免疫印迹法检测LC3和Beclin-1的表达. 结果 动物实验中,与NC和IN组比较,IH组大鼠逃避潜伏期明显延长,且在目标象限停留时间百分比减低(均P＜0.05);IH组海马神经细胞凋亡率(12.2±3.2)％,较NC组(5.9±2.1)％和IN组(6.3±1.9)％明显升高(F=6.01,P=0.037);电镜示IH组胞核固缩的同时,双层膜结构的自噬泡增多;进一步的免疫印迹结果显示,IH组LC3和Beclin-1蛋白水平升高(均P＜0.05). 结论 间歇低氧可诱导海马神经细胞凋亡和自噬表达增多,可能为间歇低氧导致认知功能障碍的可能机制之一.