经鼻给药沉香精油对单次长时间应激小鼠PTSD样行为及海马GluN2A、GluN2B表达的影响

Effect of Transnasal Administration of Agarwood Essential Oil on Posttraumatic Stress Disorder-like Behaviors and the Expression of GluN2A and GluN2B in the Hippocampus in Mice Induced by Single Prolonged Stress

目的评价经鼻给药沉香精油对单次长时间应激(single-prolonged stress,SPS)诱导的小鼠创伤后应激障碍(posttraumatic stress disorder,PTSD)样行为的作用,并从突触的角度探讨其可能的作用机制。方法通过气相色谱—质谱联用定性分析沉香精油主要成分;将C57BL/6小鼠随机分为正常组、模型组、沉香精油低剂量组、沉香精油高剂量组和阳性药组[罗利普兰(Rolipram,ROL)],每组8只。采用行为学实验评价SPS小鼠的PTSD样行为:分别通过恐惧记忆测试实验检测小鼠恐惧凝滞时间,旷场和高架十字迷宫实验评价小鼠的焦虑样行为。Western blot法检测小鼠海马组织N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR)2A亚单位(GluN2A)、2B亚单位(GluN2B)蛋白表达水平。结果沉香精油样品中共检测到117种挥发性成分。动物实验结果表明,与正常组比较,模型组小鼠表现出强烈的焦虑样行为及恐惧记忆消退异常(P<0.05),而沉香精油及阳性药ROL可明显改善SPS小鼠的异常行为(P<0.05),并逆转GluN2A、GluN2B的异常表达(P<0.05)。结论经鼻给药沉香精油对SPS诱导的小鼠PTSD样行为具有改善作用,其机制可能与调控GluN2A、GluN2B蛋白表达有关。

Objective To investigate the effect of transnasal administration of agarwood essential oil on mice with posttraumatic stress disorder(PTSD)-like behaviors induced by single prolonged stress(SPS)and its possible mechanisms from the perspective of synaptic plasticity.Methods Gas chromatography-mass spectrometry was used for qualitative analysis of the main components of agarwood essential oil.C57BL/6 mice were randomly divided into normal group,model group,low-and high-dose agarwood essential oil groups,and positive drug group,with 8 mice in each group.Behavioral experiments were used to assess the PTSD-like behaviors of SPS mice;the fear memory test was used to measure the fear freezing value of mice,and the open field test and the elevated plus maze test were used to assess anxiety-like behaviors;Western blot was used to measure the protein expression levels of GluN2A and GluN2B in the hippocampus of mice.Results A total of 117 volatile components were detected in agarwood essential oil samples.Animal experiments showed that compared with the normal group,the model group showed marked anxiety-like behaviors and significant abnormalities in fear memory extinction(P<0.05),while agarwood essential oil and the positive drug ROL significantly improved the abnormal behaviors of SPS mice(P<0.05)and reversed the abnormal expression of GluN2A and GluN2B(P<0.05).Conclusion Transnasal administration of agarwood essential oil can improve the PTSD-like behaviors of mice induced by SPS,possibly by regulating the protein expression levels of GluN2A and GluN2B.