甘麦大枣汤对PTSD模型大鼠行为学的影响及其机制研究  

Effect of Ganmai Dazao Decoction on ethology of rats with PTSD and its mechanism

作　　者：张金 董健健[4] 朱清俊 郑艳敏 童海洋 吴云[3] 王璐璐 杨鸿毅[3] 郭建友 ZHANG Jin;DONG Jian-jian;ZHU Qing-jun;ZHENG Yan-min;TONG Hai-yang;WU Yun;WANG Lu-lu;YANG Hong-yi;CUO Jian-you(Institute of Psychology,Chinese Academy of Sciences,Bejing 100101,China;Department of Psychology,University of Chinese Academy of Sciences,Beijing 100049,China;Hefei Institute of Physical Science,Chinese Academy of Sciences,Hefei 230031,China;Neurology Institute,Anhui University of Chinese Medicine,Hefei 230061,China)

机构地区：[1]中国科学院心理研究所,北京100101 [2]中国科学院大学心理学系,北京100049 [3]中国科学院合肥物质科学研究院,安徽合肥230031 [4]安徽中医药大学神经病学研究所,安徽合肥230061

出　　处：《中国中药杂志》2023年第3期762-769,共8页China Journal of Chinese Materia Medica

基　　金：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)。

摘　　要：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NPY1R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�This study aimed to explore the effect of Ganmai Dazao 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^(-1)), medium(2 g·kg^(-1)), and high-dose Ganmai Dazao Decoction groups(4 g·kg^(-1)), and the positive control group(intragastric administration with 10.8 mg·kg^(-1)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 Dazao 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 days. 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 9.4T 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 Dazao 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 Dazao 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

关 键 词：甘麦大枣汤 创伤后应激障碍 神经功能损伤 行为学 9.4T磁共振 神经保护作用 

分 类 号：R285.5[医药卫生—中药学]