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

中文关键词:  创伤后应激障碍 海马 凋亡 信号通路 大鼠

英文关键词:Post-traumatic stress disorder Hippocampus Apoptosis Signal pathway Rats

中文摘要:

      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。

英文摘要:

      【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.