甘麦大枣汤对P丁SD模型大鼠行为学的影响及其机制研究
文献类型：学位论文
| 作者 | 张金 |
| 答辩日期 | 2023-06 |
| 文献子类 | 继续教育硕士 |
| 授予单位 | 中国科学院大学 |
| 授予地点 | 中国科学院心理研究所 |
| 其他责任者 | 郭建友 |
| 关键词 | 甘麦大枣汤 创伤后应激障碍 神经肤Y 1R 9.4 T磁共振 |
| 学位名称 | 理学硕士 |
| 学位专业 | 健康心理学 |
| 其他题名 | Study on the regulatory effect of Ganmai Dazao Decoction on nerve function iniurv in PTSD model rats |
| 中文摘要 | Purpose: Posttraumatic stress disorder (PTSD) is a severe mental illness that affects an individual's physical and mental health as well as their social function after exposure to an abnormal threatening or catastrophic stress event. Currently, PTSD is mainly treated with anti-anxiety and anti-depressant medication, which often have side effects such as nausea, diarrhea, indigestion, and abdominal pain. Ganmai dazao decoction is a famous traditional Chinese medicine formula that has a calming effect on the mind, relieves urgency, and has anti-depressant effects. Modern pharmacological research has shown that it has anti-anxiety and anti-depressant effects. This study aims to explore the therapeutic effect of Ganmai dazao decoction on PTSD in rats and its relationship with the neuropeptide Y1R and brain structure in the hippocampus area, providing evidence for the pre-diagnosis and post-treatment of PTSD. Methods: In Study I, the Ganmai dazao decoction was made into lyophilized powder and divided into low, medium, and high doses of 1 g/kg, 2 g/kg, and 4 g/kg. Liquid chromatography-mass spectrometry was used to analyze the composition of Ganmai dazao decoction. The Single-Prolonged Stress (SPS) method was used to establish PTSD rat models. In Study II, rats were divided into six groups: normal group, model group, Ganmai dazao decoction low, medium, and high dose groups, and positive control group (10 rats per group). The low, medium, and high dose groups were given 1 g/kg, 2 g/kg, and 4 g/kg of Ganmai dazao decoction by gavage, respectively. The positive control group was given 10.8 mg/kg of Fluoxetine by gavage. The normal group and model group were given an equal volume of physiological saline by gavage. All groups were treated for seven consecutive days. The Open Field Test, Elevated Plus Maze Test, Forced Swimming Test, and Novel Object Recognition Test were used to investigate the effect of Ganmai dazao decoction on PTSD behavior. In Study III, Western blotting was used to determine differences in neuropeptide Y1R expression in the hippocampus area of rats from different groups. In Study IV, 9.4T high一field magnetic resonance imaging system was used to observe structural changes in the rat brain regions, and the hippocampus was used as the region of interest to calculate the degree of anisotropic diffusion (FA) to detect the effect of Ganmai dazao decoction on PTSD rat brain function. Results: In Study I, compounds with a comprehensive score greater than 60 were successfully screened from low, medium, and high dose Ganmai dazao decoction samples, and a total ion flow map was formed. Moreover, flavonoids, phenols, alkaloids, saponins, and other compounds with a high correlation with Ganmai dazao decoction were found. In Study II, medium and high dose Ganmai dazao decoction significantly increased the total movement distance and central zone time of PTSD rats in the Open Field Test. The results of the Elevated Plus Maze Test showed that compared with the model group, the middle and high dose Ganmai dazao decoction significantly increased the number of times and duration of open arm entry of PTSD rats. In the Forced Swimming Test, the immobility time in the model group was significantly higher than that in the normal group, but it was significantly reduced after Ganmai dazao decoction treatment. Moreover, the Novel Object Recognition Test found that Ganmai dazao decoction significantly improved the exploration time of new objects in PTSD rats. In Study III, the expression of neuropeptide Y1R in the hippocampus of the model group was significantly higher than that in the normal group, but it was significantly reduced after treatment with middle and high dose Ganmai dazao decoction and Fluoxetine. In Study IV, 9.4T MRI showed that there were no significant abnormalities in the high, low signal, and uneven signal in all rat brain regions. Regarding functional imaging, ROI analysis showed that compared with the normal group, the hippocampal FA value of the model group rats significantly decreased. Compared with the model group, the hippocampal FA value significantly increased after treatment with middle and high dose Ganmai dazao decoction and Fluoxetine. Conclusion: The above results indicate that Ganmai dazao decoction has a significant therapeutic effect on PTSD in rats, which may be due to the inhibition of neuropeptide Y1R expression in the hippocampus of PTSD model rats, alleviating PTSD model brain function damage, and improving PTSD-like behavior of anxiety and depression. |
| 英文摘要 | 目的:创伤后应激障碍(Posttraumatic stress disorder, PTSD)是个体暴露于异乎寻常的威肋、性或灾难性应激事件后，产生了持续的、严重的心理疾患，并影响到个体的身心健康和社会功能。目前，PTSD主要是通过抗焦虑、抗抑郁药物来缓解相关症状，但这些药物具有恶心、腹泻、消化不良及腹痛等副作用。甘麦大枣汤是著名的中药方剂，具有养心安神、和中缓急以及抗抑郁等功效，现代药理研究表明其具有抗焦虑和抗抑郁作用。本研究旨在探讨甘麦大枣汤对大鼠PTSD的治疗作用以及与海马区域的神经肤Y 1R和脑结构之间的关系，为PTSD的预前诊断及预后治疗提供证据。 方法:研究I将甘麦大枣汤制成冻干粉，按照1 g/kg, 2 g/kg, 4 g/kg分为低、中、高剂量，应用液质联用技术对甘麦大枣汤的成分进行分析，并采用单次延长应激(Single-Prolonged Stress, SPS)方法建立SD大鼠PTSD模型。研究II将大鼠分为6组，分别为正常组、模型组、甘麦大枣汤低、中、高剂量组和阳性对照组，每组10只，低、中、高剂量组分别给予1 g/kg, 2 g/kg, 4 g/kg甘麦大枣汤灌胃;阳性对照组，给予10.8 mg/kg氟西汀灌胃;正常组、模型组给予相同体积的生理盐水灌胃，6组均连续给药7d。应用旷场实验、高架十字迷宫实验、强迫游泳实验、新物体识别测试实验，探讨甘麦大枣汤对PTSD行为学的影响。研究III采用蛋白质印迹法测定不同组别大鼠脑部海马区域的神经肤Y 1R表达差异。研究IV运用9.4 T高场磁共振成像装置，观察大鼠脑区的结构变化，并将海马作为感兴趣区计算各向异性扩散程度(FA值)，检测甘麦大枣汤对PTSD大鼠脑功能的影响。 结果:研究I，成功筛选出了甘麦大枣汤低、中、高剂量样本综合评分大于60分的化合物，并形成了总离子流图。此外，还发现了黄酮、酚类、生物碱、皂普等与甘麦大枣汤相关度较高的化合物。研究II，中、高剂量甘麦大枣汤可显著增加PTSD大鼠旷场实验运动总路程及中央区时间。高架十字迷宫实验结果显示，与模型组相比，中、高剂量甘麦大枣汤可显著增加PTSD大鼠开臂进入次数及开臂停留时间。强迫游泳实验中，模型组大鼠不动时间显著高于正常组，但给予甘麦大枣汤后其不动时间显著降低。此外，新物体识别测试发现，甘麦大枣汤可显著提高PTSD大鼠对新物体的探索时间。研究III，模型组较正常组大鼠海马神经肤Y 1R表达显著增加，中、高剂量甘麦大枣汤和氟西汀治疗后可显著降低PTSD大鼠神经肤Y 1R表达。研究IV, 9.4T MRI检测发现，所有大鼠各脑区无明显异常的高、低信号和不均匀信号;功能像中，通过ROI分析计算发现，与正常组比较，模型组大鼠海马FA值显著下降，中、高剂量甘麦大枣汤组和氟西汀给药后，海马FA值显著升高。 结论:以上结果表明甘麦大枣汤对大鼠PTSD具有显著改善疗效，这可能是由于抑制了PTSD模型组大鼠海马神经肤Y1R表达，减轻PTSD模型脑功能损伤，从而改善PTSD模型的运动功能及焦虑抑郁样行为。 |
| 语种 | 中文 |
| 源URL | [http://ir.psych.ac.cn/handle/311026/45172]  |
| 专题 | 心理研究所_健康与遗传心理学研究室 |
| 推荐引用方式 GB/T 7714 | 张金. 甘麦大枣汤对P丁SD模型大鼠行为学的影响及其机制研究[D]. 中国科学院心理研究所. 中国科学院大学. 2023. |
入库方式： OAI收割
来源：心理研究所
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