百合疏肝安神汤对焦虑性抑郁症模型大鼠前额叶-边缘结构及GR/BDNF/NPY表达的影响

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (10): 1090-1098.

百合疏肝安神汤对焦虑性抑郁症模型大鼠前额叶-边缘结构及GR/BDNF/NPY表达的影响

杨琴¹，杜青²，赵洪庆³，王宇红^1,3，韩远山¹，杨蕙¹，孟盼³

¹湖南中医药大学第一附属医院，长沙 410007，湖南；²湖南省中医药研究所，长沙 410006，湖南；³湖南中医药大学，湖南省中药粉体与创新药物省部共建国家重点实验室培育基地，长沙 410208，湖南

收稿日期:2017-03-17 修回日期:2017-04-07 出版日期:2017-10-26 发布日期:2017-11-13
通讯作者: 王宇红，女，教授，研究员，博士生导师，研究方向：中药神经药理学。 E-mail: wyh107@126.com
作者简介:杨琴，女，硕士，研究方向：临床中药学。
基金资助:
国家自然科学基金项目（81403387）；湖南省科技厅重点项目（2015DK3003）

Effects of compound Baihe shugan anshen on stucture and expressions of GR, BDNF and NPY on prefrontal cortex-edge structure in anxious depression model rats

YANG Qin¹, DU Qing², ZHAO Hongqing³, WANG Yuhong ^1,3, HAN Yuanshan¹, YANG Hui ¹, MENG Pan ³

¹First Hospital of Hunan University of Chinese Medicine, Changsha 410007, Hunan, China；² Hunan Academy of Chinese Medicine, Changsha 410006, Hunan, China; ³ Hunan University of Traditional Chinese Medicine, Training Bases, Hunan Key Laboratory of Chinese Materia Medica Powder and Innovative Drugs Established by Provincial and Ministry, Changsha 410208, Hunan, China

Received:2017-03-17 Revised:2017-04-07 Online:2017-10-26 Published:2017-11-13

摘要/Abstract

摘要：

目的: 探讨百合疏肝安神汤对焦虑性抑郁症模型大鼠前额叶-边缘(海马、杏仁核)结构及GR/BDNF/NPY表达的影响。方法: 将SD大鼠按体质量随机分为7组：焦虑性抑郁模型组、阳性药（文拉法辛6.75 mg/kg）组、百合疏肝安神汤高（24.28 g/kg）、中（12.24 g/kg）、低（6.12 g/kg）剂量组，另设空白对照组和溶媒组；连续21 d慢性束缚应激＋孤笼饲养，并皮下注射皮质酮（30 mg/kg）复制焦虑性抑郁症动物模型，造模同时灌胃给药，溶媒组皮下注射生理盐水+5%DMSO，空白对照组正常饲养。采用HE染色检测前额叶皮层、海马、杏仁核结构形态变化；Western blotting法测定糖皮质激素受体（glucocorticoid, GR）、脑源性神经营养因子（brain derived neurotrophic factor, BDNF）和神经肽Y（neuropeptide Y, NPY）的表达。结果: 与空白对照组比较，焦虑性抑郁模型大鼠前额叶皮层胶质细胞增多，神经元细胞数量减少，椎体神经元发生空泡样改变，细胞核萎缩；海马DG区和CA3区神经元丢失，CA3区神经元细胞核出现深染；杏仁核神经元细胞核边界模糊，细胞排列散乱，细胞数量明显减少；前额叶皮层、海马、杏仁核中GR、BDNF、NPY蛋白表达均显著降低（P<0.05或P<0.01）。与模型组比较，百合疏肝安神汤高剂量组大鼠前额叶皮层神经胶质细胞增生情况明显缓解，细胞排列较整齐；海马DG区和CA3区神经元细胞增多，CA3区神经元损伤减轻；杏仁核神经元损伤减轻；百合疏肝安神汤高剂量组大鼠前额叶皮层、海马、杏仁核中GR、BDNF、NPY蛋白表达均明显升高（P<0.05或P<0.01）。结论: 百合疏肝安神汤抗焦虑抑郁作用可能与调节GR/BDNF/NPY信号级联反应，保护前额叶边缘（海马、杏仁核）结构损伤有关。

关键词: 焦虑性抑郁, 百合疏肝安神汤, 前额叶-边缘结构, 糖皮质激素, 脑源性神经营养因子, 神经肽Y

Abstract:

AIM: To investigate the effects of compound Baihe shugan anshen on anxiety depression model rat prefrontal cortex-edge(hippocampus and amygdala) structure and expression of GR/BDNF/NPY. METHODS: SD rats were randomly divided into 7 groups according to body weight: the anxious depression model group, the positive drug (venlafaxine 6.75 mg/kg) group, the compound Baihe shugan anshen-high, -middle, -low (24.28 g/kg, 12.24 g/kg, 6.12 g/kg) group, the control group and the vehicle group. Chronic restraint stress plus solitary feeding and subcutaneous injection of CORT (30 mg/kg) for 21 d were administered to build the animal model of anxiety depression. At the same time, the positive drug group and compound Baihe shugan anshen group received intragastric administration. The vehicle group received subcutaneous injection of physiological saline plus 5%DMSO. The control group was fed normally. Morphological changes of prefrontal cortex (PFC), hippocampus and amygdala were analyzed by HE staining, and determination of GR, BDNF and NPY by Western blotting. RESULTS: Compared with the blank control group, glial cells were increased while the neurons were decreased; vertebral neurons were physalides, and nucleus were wither in PFC of anxiety-depression rats. Neurons in hippocampal DG and CA3 area were lost, and the nucleus of neurons in CA3 area was deeply stained. The nucleus of amygdala neurons was fuzzy, the cells were scattered, and the number of cells were decreased significantly. The levels of GR, BDNF and NPY in PFC, hippocampus and amygdala were significantly decreased (P<0.05 or P<0.01). Compared with the model group, prefrontal cortex glial cell proliferation was obviously relieved; cells were arranged in order in the Baihe shugan anshen high dose group. Neurons in hippocampus DG and CA3 were increased and CA3 neurons recovered. The damage of neurons in the amygdala was also reduced. The levels of GR, BDNF and NPY in PFC, hippocampus and amygdala were significantly increased (P<0.05 or P<0.01). CONCLUSION: The anti-anxiety and depression effect of Baihe shugan anshen may be related to the cascade of regulation of GR/BDNF/NPY signal to protect the prefrontal-marginal(hippocampus,amygdala) structural injury.

Key words: anxious depression, compound Baihe shugan anshen, pefrontal cortex-limbic stucture, GR, BDNF, NPY

中图分类号:

R285.5

杨琴，杜青，赵洪庆，王宇红，韩远山，杨蕙，孟盼 . 百合疏肝安神汤对焦虑性抑郁症模型大鼠前额叶-边缘结构及GR/BDNF/NPY表达的影响[J]. 中国临床药理学与治疗学, 2017, 22(10): 1090-1098.

YANG Qin, DU Qing, ZHAO Hongqing, WANG Yuhong, HAN Yuanshan, YANG Hui, MENG Pan. Effects of compound Baihe shugan anshen on stucture and expressions of GR, BDNF and NPY on prefrontal cortex-edge structure in anxious depression model rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(10): 1090-1098.

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