Xiaoyaosan Ameliorates Chronic Immobilization Stress-Induced Depression-Like Behaviors and Anorexia in Rats: The Role of the Nesfatin-1-Oxytocin-Proopiomelanocortin Neural Pathway in the Hypothalamus
Xiaoyaosan Ameliorates Chronic Immobilization Stress-Induced Depression-Like Behaviors and Anorexia in Rats: The Role of the Nesfatin-1-Oxytocin-Proopiomelanocortin Neural Pathway in the Hypothalamus
复制标题
逍遥散改善大鼠慢性固定应激诱发的抑郁样行为和厌食症：下丘脑 Nesfatin-1→催产素→阿片黑皮素原神经通路的作用
DOI：
10.3389/fpsyt.2019.00910
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发表时间：
2019-12-10
影响因子：
4.7
通讯作者：
Chen, Jiaxu
中科院分区：
文献类型：
--
作者：
Ma, Qingyu;Li, Xiaojuan;Chen, Jiaxu
背景：慢性应激是抑郁症的重要危险因素。参与应激反应的nesfatin-1（NES 1）-催产素（OT）-阿黑皮素原（POMC）神经通路最近被证明在下丘脑中具有厌食作用。我们前期的研究表明，中药抗抑郁药逍遥散能有效缓解慢性固定应激（CIS）引起的食欲减退。然而，逍遥散是否通过调节NES 1-OT-POMC神经通路来改善抑郁样行为和厌食症尚不清楚。目的：探讨逍遥散抗抑郁样和抗厌食作用是否与下丘脑NES 1-OT-POMC神经通路有关。方法：将大鼠随机分为对照组、CIS组、逍遥散治疗组和氟西汀治疗组。CIS、逍遥散治疗组和氟西汀治疗组大鼠连续21天进行CIS，在此期间，通过管饲法分别给予蒸馏水、逍遥散煎剂[3.854 g/（kg中心点d）]或氟西汀[1.76 mg/（kg中心点d）]，并每天监测其体重和摄食量。随后对大鼠进行旷场试验和蔗糖偏好试验。采用实时荧光定量聚合酶链反应、免疫印迹法和免疫组化法检测血清中皮质酮和NES 1的表达水平以及下丘脑中NES 1、OT、POMC和黑素皮质素-4受体（MC 4 R）的表达水平。免疫荧光双标法检测下丘脑NES 1-OT-POMC神经通路相关蛋白的表达。结果如下：与对照组大鼠相比，暴露于CIS的大鼠表现出逐渐减少的食物摄入量和降低的体重，并显着增加血清和室旁核中的NES 1浓度。CIS组下丘脑POMC、OT和MC 4 R的表达水平显著高于对照组。逍遥散和氟西汀预处理可逆转上述变化。具体而言，逍遥散治疗组中NES 1-OT-POMC神经通路成员的表达水平低于CIS组。结论：逍遥散通过调节下丘脑NES 1-OT-POMC神经通路改善CIS诱导的抑郁样行为和厌食。
Background: Chronic stress is an important risk factor for depression. The nesfatin-1 (NES1)-oxytocin (OT)-proopiomelanocortin (POMC) neural pathway, which is involved in the stress response, was recently shown to have an anorectic effect in the hypothalamus. Our previous study showed that Xiaoyaosan, a well-known antidepressant used in traditional Chinese medicine, effectively relieved appetite loss induced by chronic immobilization stress (CIS). However, whether Xiaoyaosan ameliorates depression-like behaviors and anorexia by regulating the NES1-OT-POMC neural pathway remains unclear. Objective: To investigate whether the antidepressant-like and anti-anorexia effects of Xiaoyaosan are related to the NES1-OT-POMC neural pathway in the hypothalamus. Methods: Rats were randomly divided into control, CIS, Xiaoyaosan treatment, and fluoxetine treatment groups. The rats in the CIS, Xiaoyaosan treatment, and fluoxetine treatment groups were subjected to CIS for 21 consecutive days, during which they were administered distilled water, a Xiaoyaosan decoction [3.854 g/(kg center dot d)] or fluoxetine [1.76 mg/(kg center dot d)], respectively, by gavage, and their body weights and food intake were monitored daily. The rats were subsequently subjected to the open field test and sucrose preference test. Then, the expression levels of corticosterone and NES1 in the serum and the expression levels of NES1, OT, POMC, and melanocortin-4 receptor (MC4R) in the hypothalamus were determined by real-time fluorescence quantitative polymerase chain reaction, Western blot analysis, and immunochemistry. Furthermore, immunofluorescence double staining was used to determine whether related proteins in the hypothalamic NES1-OT-POMC neural pathway were co-expressed. Results: Compared to control rats, rats exposed to CIS exhibited gradually less food intake and lower body weights and significantly increased concentrations of NES1 in the serum and paraventricular nucleus. Moreover, the expression levels of POMC, OT, and MC4R in the hypothalamus were significantly higher in the CIS group than those in the control group. However, these changes were reversed by pretreatment with Xiaoyaosan and fluoxetine. Specifically, the expression levels of members of the NES1-OT-POMC neural pathway were lower in the Xiaoyaosan-treated group than in the CIS group. Conclusion: Xiaoyaosan ameliorates CIS-induced depression-like behaviors and anorexia by regulating the NES1-OT-POMC neural pathway in the hypothalamus.