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创伤后应激障碍大鼠海马神经元凋亡和Akt/mTOR信号通路的改变

Alteration of Apoptosis and Akt/mTOR Signal Pathway in Hippocampal Neurons of Rat with Post-traumatic

  • 摘要: 目的 检测创伤后应激障碍(PTSD)模型大鼠海马神经元凋亡和蛋白激酶B(Akt)/哺乳动物雷帕霉系靶蛋白(mTOR)信号通路的改变,探讨PTSD发病机制。方法 将成年健康雄性SD大鼠60只分为对照组(n=10)和模型组(n=50)。采用改良的单一连续应激方法制备PTSD大鼠模型,在造模后1 d、4 d、7 d、14 d和28 d处死大鼠(每个时间点处死5只),流式细胞术检测海马神经元凋亡率,Western blot方法检测海马第10号染色体缺失性磷酸酶张力蛋白同源物基因编码产物(PTEN)、磷酸化Akt(p-Akt)、磷酸化mTOR(p-mTOR)的表达水平。 结果 PTSD后1 d、4 d、7 d和14 d大鼠海马神经细胞凋亡率高于对照组(P<0.05);PTSD后1 d大鼠海马PTEN蛋白表达高于对照组(P <0.05),4 d达高峰,14 d仍高于对照组(P<0.05);p-Akt蛋白表达水平在PTSD后1 d即低于对照组(P<0.05),以后逐渐增高,28 d仍低于对照组(P<0.05);p-mTOR蛋白在PTSD后4 d低于对照组(P<0.05),以后逐渐增高,但28 d仍低于对照组(P<0.05)。结论 PTSD模型大鼠海马神经元Akt/mTOR信号通路激活,参与海马神经元凋亡调控。

     

    Abstract: 【Abstract】 Objective To observe the changes of apoptosis and protein kinase B/the mammalian target of Rapamycin (Akt/mTOR) signal pathway in hippocampal neurons of rat with post-straumatic stress disorder (PTSD), and to investigate the mechanism of PTSD. Methods Sixty male adult SD rats were divided into control group (n=10) and PTSD (n=50) model group. The PTSD animal model was established by giving the rats single-prolonged stress followed a single inescapable electric foot shock (SPS & S). The neuronal apoptosis of hiappocampus of PTSD rats at 1 d, 4 d, 7 d, 14 d and 28 d after model established was detected by flow cytometry (FCM). The expressions of phosphatase and tensin homology deleted on chromosome Ten (PTEN), phosphorylation of ARt and mTOR (p-Akt and p-mTOR) protein were detected by Western blotting. Results The apoptotic cell rate in PTSD 1 d, 4 d, 7 d and 14 d rats were higher than that in control rats (P<0.05). The PTEN expression level was higher since PTSD 1 d than that in control group, and peaked in PTSD 4 d (P<0.05). The p-Akt expression level was lower in PTSD 1 d than that in control group, and then increased in various time points after PTSD, but it was still lower in PTSD 28 d (P<0.05). The p-mTOR expression level was lower than that in control group since PTSD 4 d, and then increased in various time points after PTSD 4 d, but it was still lower in PTSD 28 d (P<0.05). Conclusion The Akt/mTOR signal pathway was actived in hippocampal neurons of PTSD rats, and which was involved in neuronal apoptosis regulation.

     

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