间歇性低氧对大鼠学习记忆功能和海马超微结构的影响

发布时间：2018-02-14 11:55

本文关键词： 间歇性低氧阻塞性睡眠呼吸暂停低通气综合征学习记忆功能海马超微结构水迷宫　出处：《华北煤炭医学院》2010年硕士论文　论文类型：学位论文

【摘要】：目的: 通过模拟OSAHS的发病特征,建立大鼠间歇性低氧(IH)模型,观察5%间歇低氧条件下,不同暴露时间过程对大鼠的学习记忆功能的影响和海马CA1区超微结构的改变,为研究OSAHS引起的认知功能损害提供实验基础。方法: 选择成年雄性Wistar大鼠(体重约170±10g)48只,随机均分为2组:空白对照组(UC组)和5%间歇性低氧组(5%IH组),UC组放入舱内给予压缩空气,IH组大鼠每日放入自制的低氧舱内暴露8小时,分别暴露2、4、6、8周。各组大鼠均常规饲养。在实验结束后进行Morris水迷宫实验;利用光镜和电镜观察海马组织结构和超微结构的变化。结果: 1、Morris水迷宫测试成绩:①定位航行实验:各组大鼠的逃避潜伏期均随实验天数延长而逐渐缩短,不同天数之间比较,逃避潜伏期有明显差异(P0.05)。IH各组逃避潜伏期随着缺氧时间延长呈逐渐延长趋势。不同暴露组之间及与对照组的逃避潜伏期比较不完全相同。5%IH2周组与6周、8周组比较,4周组与8周组比较差异显著(P0.05),其它各组内比较无差异明显(P0.05)。②Morris水迷宫记忆成绩:⒈跨越目标象限时间:各CIH组随着低氧时间延长和低氧浓度的降低,跨越目标象限时间呈逐渐缩短趋势。IH组与UC组之间比较有显著差别(P0.05)。5%CIH2周组和4、6、8周组比较差异显著(P0.05);⒉穿台次数:采用非参数检验(秩和检验),不同暴露条件之间以及不同暴露时间之间不完全相同,随着间歇低氧浓度的降低,穿台次数减少,P0.01。 2、光镜下海马组织结构的变化随着间歇低氧时间的延长,早期表现为核固缩呈强嗜碱性,核染色质聚集在核膜下呈环状,晚期凋亡表现为核溶解碎裂等,尼氏体结构逐渐变模糊并发生崩解。随着暴露时间的延长神经元数量减少。亦可见肿胀神经元细胞,表现为细胞空泡化,透亮度增高,胞浆成分不明显。3、电镜观察可见正常海马神经元核核大而圆,核仁清晰,核质均匀散在,核膜光滑,边缘清晰,细胞器丰富完整。间歇低氧组随着暴露时间的延长,海马神经元早期表现为细胞核形态变化不明显,糖原颗粒减少。后期出现核沟,并逐渐加深加大,染色质边集。细胞器逐渐减少,线粒体空泡化并出现异型结构,粗面内质网表面的脱颗粒现象逐渐加重。神经元数量减少。突触结构随暴露时间逐渐出现突触小泡增大,结构模糊,突触间隙增宽。暴露至6周时脱髓鞘现象达高峰。各时间段血管均有不同程度的水肿。结论: 1、间歇性低氧可造成大鼠学习记忆功能的降低。随着暴露时间的延长,大鼠学习记忆功能损害呈现逐渐加重趋势,慢性间歇性低氧在暴露一定时间后出现明显的学习记忆功能障碍。 2、间歇性低氧可引起海马神经元的损害,随着暴露时间的延长而逐渐加重。
[Abstract]:Objective:. The intermittent hypoxic OSAHS model was established by simulating the pathogenesis of OSAHS in rats. The effects of 5% intermittent hypoxia on the learning and memory function of rats and the ultrastructure of hippocampal CA1 were observed. To provide experimental basis for the study of cognitive impairment induced by OSAHS. Methods:. 48 adult male Wistar rats (weight about 170 卤10g / g) were randomly divided into two groups: control group (UUC group) and 5% intermittent hypoxia group. Rats in the 5% intermittent hypoxia group were exposed to hypoxia for 8 hours daily. At the end of the experiment, the Morris water maze test was carried out, and the changes of hippocampal tissue structure and ultrastructure were observed by light and electron microscopy. Results:. (1) Morris water maze test score of 1: 1 navigation experiment: the escape latency of rats in each group was shortened with the prolongation of experimental days, and was compared among different days. There was a significant difference in escape latency between P0.05 and IH groups with the prolongation of hypoxic time. The escape latency of different exposure groups and control group was not exactly the same. 5IH2 week group and 6-week 8 week group were different. There was significant difference between the 4th week group and the 8-week group (P 0.05), but there was no significant difference in the other groups. The memory score of the water maze: 1: 1 crossed the target quadrant time: each CIH group with the increase of hypoxic time and the decrease of hypoxic concentration. The time of crossing the target quadrant was gradually shortened. There was significant difference between IH group and UC group. There were significant differences between the two groups (P0.05N. 5CIH _ 2 week group and 4o 66-week group). The number of platform penetration was significant (P 0.05): nonparametric test was used (rank sum test, different exposure conditions were compared with each other). And different exposure times, With the decrease of intermittent hypoxia concentration, the number of table penetration decreased (P 0.01). 2. Changes of hippocampal tissue structure under light microscope. With the prolongation of intermittent hypoxic time, nuclear pyknosis appeared as strong basophilic in the early stage, nuclear chromatin gathered under the nuclear membrane in the annular shape, and late apoptosis appeared as nuclear dissolution and fragmentation, etc. The structure of Nissl's body gradually became blurred and disintegrated. The number of neurons decreased with the prolongation of exposure time. The cytoplasmic components were not obvious. The electron microscopic observation showed that the nucleus of normal hippocampal neurons was large and round, the nucleoli were clear, the nucleus was evenly dispersed, the nuclear membrane was smooth, the edge was clear, and the organelle was abundant and complete. In the early stage of hippocampal neurons, the nuclear morphology was not obvious, the glycogen granules were decreased, the nuclear sulcus appeared in the later stage, the chromatin side set was gradually increased, the organelle was gradually decreased, the mitochondria vacuolated and appeared abnormal structure. The degranulation of rough endoplasmic reticulum (ER) surface was gradually aggravated, and the number of neurons decreased. The synaptic vesicles gradually increased with the exposure time, and the structure of synaptic vesicles was blurred. The demyelinating phenomenon reached its peak after 6 weeks of exposure, and the blood vessels showed various degrees of edema at each time point. Conclusion:. 1. Intermittent hypoxia induced the decrease of learning and memory function in rats. With the prolongation of exposure time, the impairment of learning and memory in rats showed a tendency to aggravate gradually. Chronic intermittent hypoxia after a certain period of exposure to significant learning and memory impairment. 2. Intermittent hypoxia may cause damage to hippocampal neurons, which is aggravated with the prolongation of exposure time.
【学位授予单位】：华北煤炭医学院
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R363

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