慢性间歇性缺氧对认知功能及海马CA1区IGF-1表达的影响

The Effect of Chronic Intermittent Hypoxia on Cognition and the Expression of Insulin-like Growth Factor-1 in CA1 Region of Hippocampus

目的:探讨慢性间歇性缺氧对SD大鼠认知功能及海马CA1区IGF-1表达的影响。方法:选取16只SD成年雄性大鼠,随机分为空白组(unhandled control group,UC)和慢性间歇性缺氧组(chronic intermittent hypoxia group,CIH),UC组正常饲养,CIH组每日间歇缺氧7小时,建立慢性间歇性缺氧模型,8周结束实验,所有大鼠在实验结束后进行Morris水迷宫测试,检测其学习和记忆能力,并利用免疫组化及图像分析测定大鼠海马CA1区IGF-1蛋白的表达。结果:①Morris水迷宫学习成绩(定位航行实验):第5天训练结束时,CIH组大鼠逃避潜伏期明显长于UC组,两组之间差异有统计学意义(P<0.05);②Morris水迷宫记忆成绩:CIH组的穿越平台次数(1.38±0.92)次较UC组显著减少[(3.75±1.04),P<0.01];CIH组在跨越目标象限时间占整个游泳的时间百分率(20.52±3.41)也较UC组显著减少[(39.89±5.63),P<0.01];③CIH组大鼠海马CA1区IGF-1蛋白的表达较UC组减少(P<0.05);④大鼠海马CA1区IGF-1表达和认知功能损害程度呈负相关(r=0.867,P<0.01)。结论:①慢性间歇性缺氧可导致大鼠认知功能下降;②慢性间歇性缺氧可导致大鼠海马CA1区IGF-1的表达减少;③IGF-1对慢性间歇性缺氧大鼠认知功能损害可能具有保护作用。

Objective： To study the effect of chronic intermittent hypoxia on cognitive functions in Sprague-Dawley rats and the expression of Insulin-like Growth Factor-1 in CA1 region of hippocampus. Methods： Experiments were performed on 16 three-month-old male Sprague-Dawley rats, They were randomly assigned to two experimental groups （n=8/group）： chronic intermittent hypoxia group （CIH）, and unhandled control group （UC）. Rats in UC group were raised normally, and those in CIH group suffered 7H intermittent hypoxia everyday, The duration of experiment was 8 weeks. The learning and memory ability of rats in each group were assessed with the Morris water maze test at the end of the experiments. The expression of Insulin-like Growth Faetor-1 in CA1 region of hippocampus was investigated by immunohistochemistry staining and image analysis. Results： ①Morris water maze test learning scores （place navigation）： After 5 ＇days training, the escape latency in CIH rats was significantly longer than that in UC rats （P〈0.05）; ②Morris water maze test memory scores： The number of times of crossing the platform in CIH group （1.38±0.92） was significantly reduced than that in UC group [（3.75±1.04）, P〈0.01]; The percentage of time spent on crossing the target quadrant to the total swimming time in CIH group （20.52±3.41） was also significantly decreased compared with that in UC group [（39.89±5.63）, P〈0.01]; ③The expression of Insulin-like Growth Factor-1 in CA 1 region of hippecampus in CIH was fewer than that in UC group （P〈0.05）; ④There was negative correlation between cognition impairment in rats and the expression of IGF-1 in CA1 region of hippecampus. Conclusion： ①Chronic intermittent hypoxia can lead to cognitive impairment of the rats. ②the expression of Insulin-like Growth Factor-1 in CA1 region of hippoeampus reduced due to Chronic intermittent hypoxia. ③ IGF-1 may be of some protection for cognitive function impairment from chronic intermittent hypoxia.