丹栀逍遥散对焦虑模型大鼠行为学及线粒体形态和功能的作用研究  

Effect of Danzhi Xiaoyao Powder on behavior and mitochondrial morphology and function of anxiety model rats

作　　者：赵安然 王思琪 赵振武 郭建友[1,2] ZHAO An-ran;WANG Si-qi;ZHAO Zhen-wu;GUO Jian-you(Institute of Psychology,Chinese Academy of Sciences,Beijing 100101,China;University of Chinese Academy of Sciences,Beijing 100101,China;Third Affiliated Hospital,Beijing University of Chinese Medicine,Beijing 100029,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,北京100101 [3]北京中医药大学第三附属医院,北京100029

出　　处：《中国中药杂志》2022年第20期5584-5590,共7页China Journal of Chinese Materia Medica

基　　金：北京中医药大学青年教师基金项目(2019-JYB-JS-189);中国科学院心理健康重点实验室开放课题(KLMH2018K03)。

摘　　要：丹栀逍遥散是治疗焦虑症的经典方剂,该研究旨在研究焦虑大鼠线粒体形态功能的变化,说明丹栀逍遥散对焦虑动物模型的治疗效果及作用机制。采用不确定性空瓶饮水应激21 d建立焦虑动物模型,各组大鼠分别于应激第7、14、21天进行十字高架实验和旷场实验,检测焦虑相关蛋白指标脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)水平,评价动物的焦虑水平并初步分析丹栀逍遥散对焦虑模型大鼠的干预作用;在第21天行为学测试结束后处死动物,分离脑组织进行线粒体形态学观察,并测定线粒体功能相关指标及单磷酸腺苷依赖的蛋白激酶(adenosine 5′-monophosphate-activated protein kinase,AMPK)表达,说明丹栀逍遥散可能的作用机制。研究结果表明,丹栀逍遥散可改善动物的焦虑样行为,显著增加大鼠高架十字迷宫开臂活动比例及旷场中心区域活动时间比例,且丹栀逍遥散呈剂量依赖地提高呼吸链复合物Ⅰ、Ⅱ、Ⅲ和Ⅳ活性水平和三磷酸腺苷(adenosine triphosphate,ATP)含量,提高BDNF和磷酸化单磷酸腺苷依赖的蛋白激酶(p-AMPK)蛋白表达。电镜结果显示丹栀逍遥散治疗组杏仁核和内侧前额叶皮质细胞内线粒体线粒体嵴结构清晰,形态结构完整。该研究证明丹栀逍遥散有较好的抗焦虑作用,其机制可能与p-AMPK保护线粒体形态结构完整,维持线粒体功能水平相关。Danzhi Xiaoyao Powder is a classical prescription for anxiety.This study aims to analyze the effect of this medicine on mitochondrial morphology and function of anxiety rats and explore the mechanism of it against anxiety.Specifically,uncertain empty bottle drinking water stimulation(21 days)was employed to induce anxiety in rats.The elevated plus-maze test and open field test were respectively performed on the 7 th,the 14 th,and the 21 st days of the stimulation,so as to detect the anxiety-related protein index brain-derived neurotrophic factor(BDNF)and evaluate the anxiety level of animals.On this basis,the effect of this prescription on anxiety rats was preliminarily evaluated.After the behavioral test on the 21 st day,rats were killed and the brain tissues were separated for the observation of the mitochondrial morphology and the determination of mitochondrial function-related indicators and the adenosine 5′-monophosphate-activated protein kinase(AMPK)level.The results showed that Danzhi Xiaoxiao Powder could alleviate the anxiety-like behavior of rats,significantly increase the percentage of time in open arm in elevated plus-maze test and the ration of activity time in the central area of the field,dose-dependently raise the activity levels of respiratory chain complexⅠ,Ⅱ,ⅢandⅣand the adenosine triphosphate(ATP)content,and elevate the levels of BDNF and phosphorylated AMPK(p-AMPK).Clear structure and intact morphology of mitochondrial cristae in medial prefrontal cortex cells and amygdala were observed in the Danzhi Xiaoyao Powder group.In summary,Danzhi Xiaoyao Powder exerts therapeutic effect on anxiety,and the mechanism is the likelihood that p-AMPK protects the structure and maintains the function of mitochondria.

关 键 词：焦虑症 杏仁核 内侧前额叶皮质 线粒体 丹栀逍遥散 AMPK 

分 类 号：R285.5[医药卫生—中药学]