Yao Dan, He Xue, Wang Jin-Hu, Zhao Zheng-Yan
Department of Pediatric Health Care, Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2011 May;13(5):424-7.
To study the effects of PI3K/Akt signaling pathway inhibitor wortmannin on long-term learning and memory abilities in neonatal rats with hypoxic-ischemic brain damage (HIBD).
Forty-eight neonatal rats were randomly assigned to blank control (n=8), sham-operated (n=8), HIBD model (n=10), HIBD+DMSO (dimethyl sulfoxide, n=8) and HIBD+wortmannin groups (n=8). Wortmannin (2 μL) was injected to the left hippocampus 30 minutes before HIBD inducement in the HIBD+wortmannin group. The Morris water maze test was used to examine the long-term learning and memory abilities at the age of 28 days.
With the increased number of swimming, the escape latency was shortened in various groups. From the second day, the escape latency in the HIBD+wortmannin group was significantly longer than that in the sham-operated and the blank control groups (P<0.05), and the differences increased with the time. On the fourth day, there were significant differences in the escape latency between the HIBD+wortmannin group and the HIBD+DMSO group as well as the HIBD model group (P<0.05). On the eighth day (retention trial), there were the most obvious differences in the escape latency between the HIBD+wortmannin group with the other four groups. In the space exploration test, the number of times crossing the former platform location within 120 seconds after removing the platform in the HIBD+DMSO and the HIBD model group was lower than the sham-operated and the blank control groups (P<0.05). The HIBD+wortmannin group showed lower number of times crossing the former platform location compared with the HIBD+DMSO and the HIBD model groups (P<0.05), as well as the sham-operated and the blank control groups (P<0.01).
P13K/Akt signaling pathway inhibitor wortmannin can aggravate the cognitive impairments, thus affecting adversely long-term learning and memory abilities in neonatal rats with HIBD.
研究PI3K/Akt信号通路抑制剂渥曼青霉素对缺氧缺血性脑损伤（HIBD）新生大鼠长期学习和记忆能力的影响。
48只新生大鼠随机分为空白对照组（n = 8）、假手术组（n = 8）、HIBD模型组（n = 10）、HIBD + DMSO（二甲基亚砜，n = 8）组和HIBD + 渥曼青霉素组（n = 8）。HIBD + 渥曼青霉素组在HIBD诱导前30分钟向左侧海马注射渥曼青霉素（2 μL）。采用Morris水迷宫试验检测28日龄时的长期学习和记忆能力。
随着游泳次数增加，各组逃避潜伏期均缩短。从第2天起，HIBD + 渥曼青霉素组的逃避潜伏期显著长于假手术组和空白对照组（P < 0.05），且差异随时间增加。第4天，HIBD + 渥曼青霉素组与HIBD + DMSO组以及HIBD模型组之间的逃避潜伏期存在显著差异（P < 0.05）。在第8天（记忆测试），HIBD + 渥曼青霉素组与其他四组之间的逃避潜伏期差异最为明显。在空间探索试验中，移除平台后120秒内，HIBD + DMSO组和HIBD模型组穿越原平台位置的次数低于假手术组和空白对照组（P < 0.05）。与HIBD + DMSO组和HIBD模型组相比（P < 0.05），以及与假手术组和空白对照组相比（P < 0.01），HIBD + 渥曼青霉素组穿越原平台位置的次数更低。
PI3K/Akt信号通路抑制剂渥曼青霉素可加重认知障碍，从而对HIBD新生大鼠的长期学习和记忆能力产生不利影响。
