School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong, China.
Anat Rec (Hoboken). 2020 Aug;303(8):2144-2153. doi: 10.1002/ar.24386. Epub 2020 Mar 16.
The functional regulation of the orexin system in the central nervous system is closely related to the occurrence and development of psychotic disorders. Abnormal changes in the lateral region of the hypothalamus are associated with the comorbidity of depression and physical symptoms, and how the traditional Chinese formula Xiaoyaosan regulates these changes may reveal aspects of the pathogenesis of depression. This study aimed to establish a rat model of depression in order to examine changes in Orexin A/OxR1 expression in the lateral region of the hypothalamus and the effects of Xiaoyaosan. Sixty specific pathogen-free (SPF) male healthy Sprague-Dawley (SD) rats were used in the experiment and randomly divided into the control group, the model group, the Xiaoyaosan group and the fluoxetine group. The depression model was established by 21-day chronic immobilization stress (CIS). Food intake and body weight were recorded, and the sucrose preference test (SPT) and open field test (OFT) were used to evaluate the model. Then, the expression of Orexin A/OxR1 in the hypothalamus was measured by ELISA, Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The expression of Orexin A and OxR1 in the lateral hypothalamic area was significantly down regulated in the model group, compared with the control group. Xiaoyaosan significantly reversed these changes with obvious curative effects. Abnormal changes in Orexin A/OxR1 in the lateral hypothalamic area of rats with depression caused by chronic stress are closely related to the pathogenesis of depression accompanied by physical symptoms. Xiaoyaosan can improve depression accompanied by physical symptoms by regulating Orexin A/OxR1.
中枢神经系统中食欲素系统的功能调节与精神障碍的发生和发展密切相关。下丘脑外侧区的异常变化与抑郁和躯体症状的共病有关，而小柴胡汤如何调节这些变化可能揭示了抑郁发病机制的某些方面。本研究旨在建立抑郁大鼠模型，以研究下丘脑外侧区 Orexin A/OxR1 表达的变化以及小柴胡汤的作用。
实验采用 60 只 SPF 雄性健康 SD 大鼠，随机分为对照组、模型组、小柴胡汤组和氟西汀组。采用 21 天慢性束缚应激（CIS）建立抑郁模型。记录食物摄入量和体重，采用蔗糖偏好试验（SPT）和旷场试验（OFT）评估模型。然后通过 ELISA、Western blot 和实时定量聚合酶链反应（qRT-PCR）分析测量下丘脑 Orexin A/OxR1 的表达。
与对照组相比，模型组大鼠下丘脑外侧区 Orexin A 和 OxR1 的表达明显下调。小柴胡汤能明显逆转这些变化，疗效明显。慢性应激引起的抑郁大鼠下丘脑外侧区 Orexin A/OxR1 的异常变化与伴有躯体症状的抑郁发病机制密切相关。小柴胡汤通过调节 Orexin A/OxR1 可以改善伴有躯体症状的抑郁。
