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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 被引量:6

Alteration of Apoptosis and Akt/mTOR Signal Pathway in Hippocampal Neurons of Rat with Post-traumatic Stress Disorder
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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1d、4d、7d、14d和28d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1d、4d、7d和14d大鼠海马神经细胞凋亡率高于对照组(P<0.05);PTSD后1d大鼠海马PTEN蛋白表达高于对照组(P<0.05),4d达高峰,14d仍高于对照组(P<0.05);p-Akt蛋白表达水平在PTSD后1d即低于对照组(P<0.05),以后逐渐增高,28d仍低于对照组(P<0.05);p-mTOR蛋白在PTSD后4d低于对照组(P<0.05),以后逐渐增高,但28d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。 Objective To observe the changes of apoptosis and protein kinase B/the mammalian target of Rapamycin (Akt/mTOR) signal pathway in hippoeampal 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 singleprolonged 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 eytometry (FCM). The expressions of phosphatase and tensin homology deleted on chromosome Ten (PTEN), phosphorylation of ARt and roTOR (p-Akt and p-roTOR) 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-roTOR 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 aetived in hippoeampal neurons of PTSD rats, and which was involved in neuronal apoptosis regulation.
出处 《四川大学学报(医学版)》 CAS CSCD 北大核心 2014年第2期221-224,共4页 Journal of Sichuan University(Medical Sciences)
基金 国家自然科学基金(No.81201048) 河北省自然科学基金(No.H2012401009)资助
关键词 创伤后应激障碍 海马 凋亡 信号通路 大鼠 Post-traumatic stress disorder Hippocampus Apoptosis Signal pathway Rats
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参考文献15

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