The expression of PI3K/AKT pathway and the correlation with cognitive impairment after HIBD in rats
首发时间:2012-02-28
Abstract:Since the phosphoinositid 3-kinase/Akt (PI3K/Akt) signaling pathway and PTEN gene have been known to be closely related to hypoxia-ischemia brain injury, we hypothesized that they are involved in neonatal hypoxic ischemic brain damage (HIBD) and as well as cognitive impairment. To test this hypothesis, 7 day old newborn rats were subjected to HIBD by ligating the common carotid artery followed by hypoxia. Rat brains were collected to detect the expression of PI3K/Akt and PTEN using Western blot analysis. The expression of p-Akt and p-PTEN were found to be significantly upregulated after hypoxia-ischemia (HI) compared with the sham operation group. However the expression of p-Akt peaked at 4h, earlier than p-PTEN which is at 12h. p-Akt protein was significantly inhibited after blocking the PI3K/Akt signaling pathway using a specific inhibitor called wortmannin. Through the Morris Water Maze (MWM) test, showed that the rats' learning and memory cognitive abilities were impaired after HI, and the cognitive impairment were more severe after blocking the PI3K/Akt signaling pathway. Our findings suggest that the PI3K/Akt signaling pathway and PTEN gene play important roles to cognitive impairment in HIBD.
keywords: Neonatal rat;Hypoxia-ischemic PI3K/Akt PTEN Inhibitor Morris water maze
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大鼠缺氧缺血性脑损伤后PI3K/AKT信号通路的表达和与认知障碍的相关性
摘要:已经发现PI3K/Akt信号通路、PTEN基因与大脑缺氧缺血密切相关,为此我们进一步研究他们与新生大鼠缺氧缺血性脑损伤HIBD及认知功能障碍的关系。新生7日龄SD大鼠动脉结扎后缺氧制作新生大鼠HIBD动物模型,后处死动物取脑组织,应用Western blot检测AKT、p-Akt及p-PTEN蛋白的含量。脑缺氧缺血损伤后早期p-Akt和p-PTEN与假手术组表达比较都有不同程度的表达增加,其中p-Akt高峰较早,在4h,而p-PTEN的高峰稍延迟,在12小时。应用PI3K/Akt信号通路抑制剂Wortmannin干预HIBD组的p-Akt蛋白的表达明显下降。通过水迷宫实验, Wortmannin干预HIBD组的学习记忆能力显著低于HIBD组和DMSO干预照HIBD组,同时非常显著低于假手术组和空白对照组。可见缺氧缺血后大脑海马PI3K/Akt信号通路、PTEN的表达与认知障碍密切相关。
关键词: 新生大鼠 缺氧缺血 PI3K/Akt; PTEN;抑制剂 水迷宫
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