创伤后应激障碍大鼠海马与前额叶皮质中OREXIN受体的失调

目的:从食欲素(Orexin, ORX)系统挖掘创伤后应激障碍的神经生物学机制。方法:以单次延长刺激(single prolonged stimulation,SPS)法复制创伤后应激障碍(post traumatic stress disorder,PTSD)大鼠模型,以行为学结合血清中皮质酮和神经元特异性烯醇化酶进行模型评价,通过酶联免疫吸附试验(Elisa)分析大鼠血清与脑脊液中OREXIN水平,以实时荧光定量聚合酶链反应(RT-PCR)检测海马与前额叶皮质中的Orexin受体基因表达。结果:实验成功的复制了PTSD模型,与对照组相比,模型组大鼠血清中皮质酮和神经元特异性烯醇化酶的含量均极显著升高(P0.01),脑脊液中Orexin A、Orexin B的含量均显著升高(P0.01),海马和皮质中ORX1R与ORX2R均极显著下降(P0.01)。结论:PTSD大鼠的应激损伤与Orexin及其受体表达水平的变化密切相关。

Imbalance of OREXIN Receptor in Hippocampus and Prefrontal Cortex of Rats with PTSD

ABSTRACT Objective: To study the changes of serum corticosterone and neuron-specific enolase in rats with post-traumatic stress disorder, as well as disorders of orexin (Orexin, ORX) receptors in cerebrospinal fluid, hippocampus and prefrontal cortex. Methods: The rat model of PTSD was established by single prolonged stimulation(SPS). Analysis of corticosterone and neuron-specific enolase in rat serum and changes of Orexin receptor in cerebrospinal fluid by enzyme-linked immunosorbent assay (Elisa). The expression of orexin receptor gene in the two brain regions was detected by real-time fluorescence quantitative polymerase chain reaction(RT-PCR). Results: The contents of corticosterone and neuron-specific enolase in serum were significantly increased (P<0.01). The levels of Orexin A and Orexin B in the cerebrospinal fluid of the model group were increased, which was significantly different from the normal group(P<0.01). And the ORX1R and ORX2R in the hippocampus and cortex of the model group were significantly decreased, which was significantly different from the normal group(P<0.01). Conclusion: PTSD resulted in the increase of corticosterone and neuron-specific enolase in serum, and its mechanism may be related to the level of orexin receptor.