缺血缺氧性脑损伤对新生3日龄幼鼠学习记忆及情感行为的影响

Effects of hypoxic-ischemic brain damage on study and memory and emotional behavior in 3-day-old neonatal rats

目的观察缺血缺氧对新生3日龄SD大鼠生长发育、学习记忆以及情感行为等的影响,建立早产儿缺血缺氧性脑白质损伤的动物模型。方法结扎幼鼠右侧颈总动脉,2 h后再置缺氧仓缺氧处理2 h;对照组仅游离右侧颈总动脉。术后不同时间点对各组存活大鼠进行生长发育评价;术后第6周开始分别用Morris水迷宫和开场实验对大鼠学习记忆能力和情感行为进行测评。结果模型组大鼠存活率为80.6%,体重增长缓慢,从生后8～28 d与对照组相比均差异具有显著性(P<0.01);31.0%模型组大鼠于7周内存在右侧眼睑持续闭合,对照组则无;同日龄8 d前翻正反射模型组大鼠所需时间较对照组长(P<0.05);Morris水迷宫实验显示模型组大鼠上台成功率较对照组显著降低(P<0.05),逃避潜伏时间较对照组明显延长(P<0.01);开场实验显示模型组大鼠后肢站立次数和中央区域驻留时间较对照组显著增加,两组间差异均存在显著性(P<0.01)。结论缺血缺氧损伤可导致新生幼鼠生长发育迟缓、学习记忆以及情感行为等障碍,用此法制作的动物模型可用于模拟新生儿缺血缺氧脑损伤的研究。

【Objective】 To investigate the effects of hypoxic-ischemia on the growth development,learning,memory and emotional behavior in the 3-day-old rats,and to establish a rat model of hypoxic-ischemic brain damage（HIBD）.【Methods】 Six pups 3-day-old rats（60 rats） were randomly divided into control group and model group.Hypoxic-ischemic brain injury was induced by ligation of right carotid artery and then staying in the 8%O2/92%N2 hypoxia installation for 2 hours.The control group underwent a sham operation without carotid artery ligation and hypoxia.The growth and development were measured in both groups at different time points.Besides,Morris water maze test and open-field test were carried out to test the memory and learning,the abilities in emotion and behavior from the sixth week on.【Results】 The survival ratio was 80.6% in model group and it was much lower than that in control group（P〈 0.01）.In model group 31.0% rats had complete disorder in eye opening within 7 weeks,which did not appear in the other group.Before 8 days,there was statistical difference in righting reflex between both groups（P〈 0.05）.Morris water maze test indicated a statistical difference between the two groups in the ratio of finding the flat（P 〈0.05）,and the escape latency significantly increased in model group compared to that in control group（P 〈0.01）.Open-field test indicated that the model group had anxiety and poor adaptability.There was a significant difference in the two groups（P〈 0.01）.【Conclusions】 The rats with ischemia-hypoxia treatment show disorder in development,behavior and cognition,which indicates that this model is available to study HIBD in neonate.