围产期缺氧缺血对大鼠学习记忆的影响及其机制探讨

Learning and memory deficits caused by perinatal hypoxia-ischemia and it′s mechanisms

目的 观察缺氧缺血 (HI)对新生大鼠远期学习记忆及海马长时程增强发生率的影响 ,探讨缺氧缺血损伤学习记忆的神经机制。方法 选择符合条件的 7日龄Wistar大鼠 49只 ,随机分为正常对照组 (n=1 5)、HI组(n =2 1 )和尼莫通治疗组 (n=1 3)。HI组经结扎左侧颈总动脉、吸入含 8%氧和 92 %氮的混合气体 2h的处理。大鼠经HI处理后给予尼莫通 (1 60 μg/kg,腹腔注射 ,每日 1次 ,共 5d)治疗的为治疗组。正常对照组给予等量生理盐水腹腔注射。至生后 80d左右对各组动物进行Y迷宫分辨学习和记忆能力测试 ,行为实验结束后每组取 5只 ,采用离体脑片电生理技术检测海马LTP的发生率。结果 HI组大鼠Y迷宫中达到学会标准前所需的训练次数为 32 .82± 8.2 2 ,明显多于对照组 (P <0 .0 1 )。 2 4h后的记忆保持率为 59.0 0 %±2 1 .32 % ,显著低于对照组 (P <0 .0 5)。尼莫通可明显提高HI大鼠的学习能力 (P <0 .0 1 ) ,但对记忆无明显效果 ;高频刺激 (HFS)前各组群峰电位 (PS)的平均幅值及平均峰潜伏期之间均无显著性差异 ,HFS后对照组PS平均幅值始终高于HI组和治疗组。HFS后HI组LTP发生率为 30 .8% ,对照组为 57% ,两组间差异显著 (P <0 .0 5) ,治疗组LTP发生率 45.5% ,较HI组有所提高 ,但差异无显著性 (P >0 .0 5)。

Objective To investigate the effect of perinatal hypoxia ischmia(HI) on long term learning and me mory in rats and the underlying mechanisms. Methods Fourty nine postnatal Wistar rats aged 7 days were randomly divided into 3 groups:the nimotop group ( n =13), in which the animals received an intraperitoneal injection of 160 μg/kg body weight of nimotop once a day for 5 days, imediately after the establishment of HI model by ligation of left common carotid artery, followed by exposure to 8% oxygen and 92% nitrogen at 37℃ for 2 hours, the HI group( n =21),and a control group( n =15) in which the animals received an injection of equivalent volume of normal saline only. When the rats reached the age of about 80 days, Y maze discrimination learning abilities and memory keeping percentage were tested, and later, the incidence of long term potentiation(LTP) of CA1 area was investigated in vitro on the hypocampal slices taken from five rats of each group using the electrophysiological technique. Results In comparing with the control group, hypoxia ischemia significantly decreased the Y maze discrimination learning abilities( P <0.01) and memory keeping percentage( P < 0.05 ). Nimotop significantly increased the learning abilities ( P <0.01) of the rats after HI, but had no effect on their memory keeping power. No significant differences of average peak potentials and the peak value of latency of the population spikes(PS) among these groups were revealed before the application of high frequency stimulation(HFS). After the application of HFS, the average peak value of the PS in the control group was consistently higher than that in HI and nimotop groups. The incidence of LTP was 30.8% after the application of HFS, significantly lower than that of the control(57%, P <0.05). This difference between the nimotop and the HI groups was not significant, although it was slightly higher in the former group. Conclusion Both learning abilities and memory keeping power may be impaired by HI, which may be correlated with the inhibition of LTP in the hyppocampal area. Nimotop may be of use to improve the learning ability, but it has no obvious beneficial effect on memory keeping.