主 办:北 京 中 医 药 大 学
ISSN 1006-2157 CN 11-3574/R

北京中医药大学学报 ›› 2021, Vol. 44 ›› Issue (5): 428-435.doi: 10.3969/j.issn.1006-2157.2021.05.007

• 中药药理 • 上一篇    下一篇

慢性轻度不可预见应激模型大鼠下丘脑食欲调节因子的变化及逍遥散的作用研究*

梁媛1, 岳利峰2, 张欢润1, 李妍1, 吴望男1, 杨婧雯1, 楚天云1, 岳广欣1#   

  1. 1 中国中医科学院中医基础理论研究所 北京 100700;
    2 北京中医药大学东直门医院
  • 收稿日期:2020-11-17 出版日期:2021-05-30 发布日期:2021-06-01
  • 通讯作者: #岳广欣,男,博士,研究员,博士生导师,主要研究方向:精神行为学病证的方证相关性研究,E-mail:yuegx73@hotmail.com
  • 作者简介:梁媛,女,博士,副研究员
  • 基金资助:
    *国家自然科学基金项目(No.81603516,No.81573846),中国中医科学院基本科研业务费优秀青年科技人才(创新类)培养专项(No.ZZ-13-YQ072),中央级公益性科研院所基本科研业务费中国中医科学院基础所自主选题项目(No.YZ202024)

Changes of appetite regulating factors in hypothalamus of rats with chronic mild unpredictable stress and the effect of Xiaoyao San on it*

Liang Yuan1, Yue Lifeng2, Zhang Huanrun1, Li Yan1, Wu Wangnan1, Yang Jingwen1, Chu Tianyun1, Yue Guangxin1#   

  1. 1 Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China;
    2 Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
  • Received:2020-11-17 Online:2021-05-30 Published:2021-06-01
  • Contact: Yue Guangxin, Researcher, Doctoral Supervisor. No.16, Nanxiaojie Street. Dongzhimennei Road, Dongcheng District, Beijing 100700. E-mail: yuegx73@hotmail.com
  • Supported by:
    National Natural Science Foundation of China (No. 81603516, No. 81573846), Fundamental Research Funds for the Central Public Welfare Research Institutes(No.ZZ-13-YQ072),National Nonprofit Institute Research Grant for Institute of Basic Theory for Chinese Medicine(No.YZ202024)

摘要: 目的 探讨慢性轻度不可预见应激抑郁模型大鼠下丘脑食欲调节因子及其受体的变化,及逍遥散抗抑郁的作用机制。方法 采用慢性轻度不可预见应激造模因素建立抑郁大鼠模型,随机分为模型组、逍遥散组与氟西汀组,每组各10只,另选10只正常大鼠作为正常对照。逍遥散以最佳给药剂量(中剂量)干预4周后,通过糖水消耗实验和新环境进食压抑实验对模型大鼠进行行为学验证;免疫组化法检测各组大鼠下丘脑食欲素及其受体、瘦素及其受体(LEPR)的变化。结果 与正常组比较,模型组大鼠1%蔗糖水消耗量、糖水消耗率、体质量与进食量均下降,差异具有统计学意义(P<0.01),进食潜伏期延长(P<0.05)。在下丘脑弓状核,模型大鼠食欲素A表达上升(P<0.01),食欲素B和瘦素表达均降低(P<0.05,P<0.01)。在下丘脑室旁核,模型大鼠食欲素A的表达也上升(P<0.01),食欲素受体1和食欲素受体2表达下降(P<0.05),瘦素及其受体LEPR的表达均降低(P<0.05,P<0.01)。逍遥散对抑郁模型大鼠的糖水消耗量、体质量、进食量有上调作用(P<0.05),降低了进食潜伏期(P<0.05),对下丘脑区食欲素A、食欲素受体1与瘦素的表达有调节作用(P<0.05,P<0.01)。氟西汀能够调节食欲素B与食欲素受体2表达(P<0.05,P<0.01)。结论 逍遥散能够通过调节中枢食欲素、瘦素水平发挥抗抑郁的功效,食欲调节因子可能是其抗抑郁的靶点之一。

关键词: 慢性轻度不可预见应激, 抑郁, 逍遥散, 食欲素, 瘦素, 大鼠

Abstract: Objective To investigate the changes of appetite regulating factors and their receptors in hypothalamus of rats with chronic mild unpredictable stress depression, and explore the antidepressant mechanism of Xiaoyao San. Methods The depression rat model was established with stimulation of chronic unpredictable mild stress factors, and they were randomly divided into the model group, Xiaoyao San group and fluoxetine group (n=10), with 10 normal rats as the normal group. After the intervention of Xiaoyao San for 4 weeks, the behavior of the model rats was verified by Sugar Water Consumption Test and Feeding Behavior Test. The changes of Orexin A, Orexin B, Orexin R1, Orexin R2, leptin and leptin receptor (LEPR) were detected by immunohistochemistry. Results Compared with the normal group, 1% sucrose water consumption, sugar water consumption rate, body weight and food intake in the model group were decreased (P<0.01), and the latency of approach to food was prolonged (P<0.05). In hypothalamic arcuate nucleus (ARC), the expression of Orexin A increased(P<0.01), while the expression of Orexin B and leptin decreased (P<0.05, P<0.01) in the model group compared with the normal group. In Paraventricular Hypothalamic Nucleus (PVN), the expression of Orexin A increased(P<0.01), while the expression of Orexin R1 and Orexin R2 decreased(P<0.05), and the expression of leptin and its receptor LEPR decreased(P<0.05, P<0.01) in the model group compared with the normal group. Xiaoyao San showed an up-regulation effect on sugar consumption, body weight, and food intake in depression model rats (P<0.05), and also had a regulatory effect on the latency of approach to food and the expression of Orexin A, Orexin R1 and leptin in hypothalamus (P<0.05, P<0.01). Fluoxetine increased the expression of Orexin B and Orexin R2 (P<0.05, P<0.01). Conclusion Xiaoyao San seems to have an antidepressant effect by regulating the levels of Orexins and leptin in the central nervous system, and appetite regulating factors may be one of its main targets for antidepressant.

Key words: chronic mild unpredictable stress, depression, Xiaoyao San, Orexins, leptin, rats

中图分类号: 

  • R285.5