重度间歇低氧大鼠学习记忆功能与氧化应激的关系

目的 通过建立重度间歇低氧动物模型,探讨OSAHS大鼠学习记忆功能与氧化应激的关系.方法 成年雄性Wistar大鼠48只,体重(170±10)g,采用随机数字法分为5％间歇性低氧组和对照组,每组又分为2、4、6和8周时间组,每组6只,其中实验组给予5％间歇低氧,并分别在2、4、6、8周进行Morris水迷宫检测学习记忆功能,随后处死大鼠,取脑组织于透射电子显微镜下观察海马区超微结构的变化,通过化学比色法测定海马组织超氧化物歧化酶(SOD)活性和丙二醛水平.结果 与对照组比较,实验组大鼠水迷宫测试大鼠逃避潜伏期时间延长、跨越目标象限时间缩短、穿台次数减少,与对照组相比差异具有统计学意义(P＜0.05);随着间歇低氧持续时间延长,实验组各时间点学习功能的改变差异组间比较差异均有统计学意义(均P＜0.05).对照组大鼠海马组织于电子显微镜下神经元结构完整,细胞器丰富,而实验组大鼠海马组织的神经元和突触数量明显减少,细胞核皱缩,突触结构模糊,突触间隙增宽,且随着暴露时间的延长,细胞损伤改变愈加明显.与对照组比较,实验组海马组织丙二醛含量明显增高,而SOD活性降低,且随间歇低氧时间延长其变化更为明显,差异有统计学意义(均P＜0.05).结论 间歇重度低氧大鼠海马组织存在氧化应激损伤,可能通过引起神经元及突触数量与结构的改变,从而导致学习记忆功能障碍,且随着缺氧时间的延长逐渐加重.

The relation of learning deficits with oxidative stress in rats exposed to severe intermittent hypoxia

Objective To observe the relations between learning memory function and oxidative stress in rats exposed to severe intermittent hypoxia (IH).Methods Adult male Wistar rats (n =48)were randomly assigned to 2 groups: untreated control group (UC) and 5％ intermittent hypoxia group (5％ IH).At 2,4,6 and 8 weeks,the learning and memory ability of the rats in each group were assessed with the Morris water maze (MWM) test.The ultrastructural changes in the hippocampus of the rats were observed with transmission electron microscopy (TEM).The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by colorimetric method.Results The water maze test showed that the rats in the 5％ IH group had prolonged latency in escaping,reduced target quadrant time in crossing and reduced frequency of crossing the platform,as compared to the UC group (P ＜ 0.05).With longer time of hypoxia,the damage became more significant.It was observed that the structure of neuron cell was complete and organelles were abundant in UC groups.With the extention of exposure time,the number of hippocampus neurons and synaptic were decreased in 5％ IH groups,nucleus shrank,synaptic frame became indefinite and synaptic cleft widen.Comparing with control group,the level of MDA in the hippocampal region group was significantly higher (P ＜0.05) and the activity of SOD significantly was lower (P ＜0.05) in 5％ IH,along with the time expand,which aggravated.Conclusion Severe intermittent hypoxia that results in learning and memory dysfunction.It is possible that oxidative stress change the quantity and structure of hippocampal neurons and synaptic,which aggravates along with the intermittent low oxygen time expand.