Ding Xiu-Fang, Li Yue-Hua, Chen Jia-Xu, Sun Long-Ji, Jiao Hai-Yan, Wang Xin-Xin, Zhou Yan
School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing, 100029, China.
Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, China.
BMC Complement Altern Med. 2017 Jun 19;17(1):326. doi: 10.1186/s12906-017-1830-0.
Xiao Yao San (XYS) is an herbal prescription which is used in the treatment of depression for thousands of years from Song dynasty in China (960-1127 A.D.), and is the bestselling and most popular herb formula for treating major depression. This study aimed to assess the chronic antidepressant effects of XYS and fluoxetine in depressed mice induced by chronic unpredictable mild stress (CUMS) and its association with alterations in glutamate/glutamine cycle and glutamate transporters.
Mice in the control and model group were given 0.5 ml physiological saline by intragastric administration. Mice in two treatment groups were given XYS (0.25 g/kg/d) and fluoxetine (2.6 mg/kg/d), respectively. The depressive-like behaviors such as forced swim test (FST), sucrose preference test (SPT) and novelty-suppressed feeding (NSF) test were measured after mice exposed to CUMS for 21 days. Body weight, contents of glutamate and glutamine, glutamine/glutamate ratio that is usually thought to reflect glutamate/glutamine cycle, and the protein and mRNA expressions of glutamate transporters (excitatory amino acid transporter 1-2,GLAST/EAAT1 and GLT-1/EAAT2) were measured. The immunoreactivities of GLAST and GLT-1 in the hippocampus were also investigated.
After CUMS exposure, mice exhibited depressive-like behaviors, body weight loss, increased glutamate level, decreased glutamine level, elevated glutamine/glutamate ratio, decreased GLT-1 protein expression and mRNA level, and decreased average optical density (AOD) of GLT-1 in the CA1, CA3 and DG in the hippocampus. These abnormalities could be effectively reversed by XYS or fluoxetine treatment. In addition, the study also found that GLAST expression in the hippocampus could not be altered by 21-d CUMS.
The studies indicated that XYS may have therapeutic actions on depression -like behavior s induced by CUMS in mice possibly mediated by modulation of glutamate/glutamine cycle and glutamate transporter GLT-1 in the hippocampus.
逍遥散（XYS）是一种中药方剂，自中国宋代（公元960 - 1127年）起已用于治疗抑郁症数千年，是治疗重度抑郁症最畅销且最受欢迎的中药配方。本研究旨在评估逍遥散和氟西汀对慢性不可预测轻度应激（CUMS）诱导的抑郁小鼠的慢性抗抑郁作用及其与谷氨酸/谷氨酰胺循环和谷氨酸转运体改变的关系。
对照组和模型组小鼠经灌胃给予0.5 ml生理盐水。两个治疗组小鼠分别给予逍遥散（0.25 g/kg/d）和氟西汀（2.6 mg/kg/d）。小鼠暴露于CUMS 21天后，测量强迫游泳试验（FST）、蔗糖偏好试验（SPT）和新奇抑制摄食（NSF）试验等抑郁样行为。测量体重、谷氨酸和谷氨酰胺含量、通常认为反映谷氨酸/谷氨酰胺循环的谷氨酰胺/谷氨酸比值，以及谷氨酸转运体（兴奋性氨基酸转运体1 - 2，GLAST/EAAT1和GLT - 1/EAAT2）的蛋白质和mRNA表达。还研究了海马中GLAST和GLT - 1的免疫反应性。
暴露于CUMS后，小鼠表现出抑郁样行为、体重减轻、谷氨酸水平升高、谷氨酰胺水平降低、谷氨酰胺/谷氨酸比值升高、GLT - 1蛋白表达和mRNA水平降低，以及海马CA1、CA3和DG区GLT - 1的平均光密度（AOD）降低。逍遥散或氟西汀治疗可有效逆转这些异常。此外，研究还发现21天的CUMS不会改变海马中GLAST的表达。
研究表明，逍遥散可能对CUMS诱导的小鼠抑郁样行为具有治疗作用，可能是通过调节海马中的谷氨酸/谷氨酰胺循环和谷氨酸转运体GLT - 1介导的。
