中国科学院心理研究所机构知识库

探讨甘麦大枣汤对创伤后应激障碍（posttraumatic stress disorder， PTSD）模型大鼠行为学的影响，通过磁共振成像和蛋白表达的变化研究相关机制。将60只大鼠随机分为6组，正常组、模型组、阳性对照组（氟西汀，灌胃给药，10.8 mg·kg~(-1)）以及甘麦大枣汤低（1 g·kg~(-1)）、中（2 g·kg~(-1)）、高（4 g·kg~(-1)）剂量组，每组10只。单次延长应激（single-prolonged stress，SPS）建立PTSD模型后2周，阳性对照组给予盐酸氟西汀胶囊灌胃，低、中、高剂量组给予甘麦大枣汤的不同剂量灌胃，正常组和模型组给予同等体积的生理盐水灌胃，连续给药7 d。旷场实验、十字高架迷宫、强迫游泳实验和新物体识别实验进行行为学测试；每组分别选择3只大鼠用蛋白质印迹法（Western blot）检测海马区神经肽受体Y1（NPY1R）蛋白表达量；再将每组的另外3只大鼠用9.4T磁共振成像实验观测脑区的整体结构变化以及海马区的各向异性分数。旷场实验结果显示，模型组大鼠总路程及中央路程较正常组显著降低，甘麦大枣汤中、高剂量组大鼠总路程及中央路程较模型大鼠显著增加；高架十字迷宫检测发现中、高剂量甘麦大枣汤可显著增加PTSD模型大鼠开臂进入次数及开臂停留时间；强迫游泳实验发现，模型组大鼠在水中不动时间显著高于正常组，甘麦大枣汤可显著降低PTSD模型大鼠水中不动时间；新物体识别测试发现，甘麦大枣汤可显著增加PTSD模型大鼠对新物体的探索时间；Western blot结果显示，甘麦大枣汤可显著降低PTSD模型大鼠海马NYP1R蛋白表达；9.4T磁共振检测发现，各组在结构像上无显著差异，而在功能像上，模型组海马体各向异性分数（FA值）显著低于正常组，甘麦大枣汤中、高剂量组大鼠海马区FA值较PTSD模型大鼠显著增加。甘麦大枣汤可通过抑制PTSD模型大鼠海马神经肽受体Y1表达，减轻海马神经元损伤，从而改善PTSD模型大鼠神经功能损伤，发挥神经保护作用。

This study aimed to explore the effect of Ganmai Dazhao Decoction on the ethology of rats with posttraumatic stress disorder (PTSD) and study the related mechanism through the changes in magnetic resonance imaging and protein expression. Sixty rats were randomly divided into 6 groups, namely the normal group, the model group, the low (1 g/kg), medium (2 g/kg), and high-dose Ganmai Dazhao Decoction groups (4 g/kg), and the positive control group (intragastric administration with 10.8 mg/kg of fluoxetine), with 10 rats in each group. Two weeks after inducing PTSD by single - prolonged stress (SPS) in rats, the positive control group was given fluoxetine hydrochloride capsule by gavage, the low, medium, and high-dose groups were given Ganmai Dazhao Decoction by gavage, and both the normal group and the model group were given the same volume of normal saline by gavage, each for 7 d. The open field experiment, elevated cross elevated maze, forced swimming experiment, and new object recognition test were carried out for the behavioral test. Three rats in each group were selected to detect the expression of neuropeptide receptor Y1 (NPY1R) protein in the hippocampus by Western blot. Then, the other three rats in each group were selected to use the 9.4 T magnetic resonance imaging experiment to observe the overall structural changes in the brain region and the anisotropy fraction of the hippocampus. The results of the open field experiment showed that the total distance and central distance of rats in the model group were significantly lower than those in the normal group, and the total distance and central distance of rats in the middle and high -dose Ganmai Dazhao Decoction groups were higher than those in the model group. The results of the elevated cross maze test showed that medium and high-dose Ganmai Dazhao Decoction remarkably increased the number of open arm entries and the residence time of open arm of rats with PTSD. The results of the forced swimming experiment showed that the immobility time in the water of the model group rats was significantly higher than that of the normal group, and Ganmai Dazhao Decoction hugely reduced the immobility time in the water of rats with PTSD. The results of the new object recognition test showed that Ganmai Dazhao Decoction significantly increased the exploration time of new objects and familiar objects in rats with PTSD. The results of Western blot showed that Ganmai Dazhao Decoction significantly reduced the expression of NYP1R protein in the hippocampus of rats with PTSD. The 9.4T magnetic resonance examination found that there was no significant difference in the structural image among the groups. In the functional image, the fractional anisotropy (FA value) of the hippo campus in the model group was significantly lower than that in the normal group. The FA value of the hippocampus in the middle and high - dose Ganmai Dazhao Decoction groups was higher than that in the model group. Ganmai Dazhao Decoction reduces the injury of hippocampal neurons by inhibiting the expression of NYP1R in the hippocampus of rats with PTS, thereby improving the nerve function injury of rats with PTSD and playing a neuroprotective role.

国家自然科学基金项目(82073971);; 安徽省重点研究和开发计划项目(201904a07020098);; 中国科学院心理研究所自主部署课题(E2CX4115CX)