姜宁, 范琳犀, 杨玉洁, 刘新民, 林海英, 高莉, 王琼
西南医科大学医学基础研究中心/药学院，泸州 646000；中国医学科学院北京协和医学院药用植物研究所，北京 100193；新疆维吾尔自治区维吾尔医药研究所，乌鲁木齐 830049
为了探讨金钗石斛提取物对慢性不可预见应激模型小鼠的抗抑郁作用，将BALB/c小鼠分为6组，即正常组、模型组、阳性药组(帕罗西汀)，金钗石斛低(50 mg/kg)、中(100 mg/kg)、高(200 mg/kg)剂量组，灌胃给药两周后，除正常组外，其他组给予慢性不可预见性应激造模35天。造模结束后，通过糖水偏爱、新奇抑制摄食、强迫游泳实验和悬尾实验检测其行为学改变，采用LC-MS/MS测定各组小鼠应激后海马及皮层单胺类神经递质包括多巴胺(dopamine, DA)和5-羟色胺(5- hydroxytryptamine, 5-HT)的含量改变。结果显示，与正常组相比，模型组小鼠糖水偏爱指数下降(P < 0.01)；与模型组比较，金钗石斛各剂量组可显著逆转模型小鼠出现的糖水偏爱指数下降(P < 0.01)，其作用与阳性药帕罗西汀相当；与正常组相比，模型组小鼠新奇抑制摄食潜伏期延长(P < 0.01)；与模型组比较，金钗石斛各剂量组均可显著缩短新奇抑制摄食潜伏期(P < 0.01)；与正常组相比，模型组小鼠悬尾的不动时间明显延长(P < 0.01)，与模型组比较，帕罗西汀及200 mg/kg金钗石斛均可缩短悬尾的不动时间(P < 0.05)；与正常组相比，模型小鼠在强迫游泳实验中不动时间无明显延长，各给药组的不动时间也未见明显改变(P > 0.05)。与正常组相比，模型组小鼠皮层和海马中的DA和5-HT含量明显减少(P < 0.05)；帕罗西汀能使模型小鼠海马和皮层DA、海马5-HT含量明显增加(P < 0.05)；金钗石斛低、高剂量组皮层DA含量与模型组相比显著性升高(P < 0.05)，金钗石斛中、高剂量组海马DA含量与模型组相比显著性升高(P < 0.05)；金钗石斛高剂量组皮层和海马5-HT含量显著高于模型组(P < 0.05)，但金钗石斛中剂量组仅海马5-HT含量显著高于模型组(P < 0.01)。以上结果提示，慢性不可预见应激可导致小鼠的类抑郁样行为出现，而金钗石斛提取物能有效改善慢性不可预见应激模型动物的抑郁样行为学表现，并提高小鼠脑内的DA和5-HT水平。
Antidepressant effects of the extract of Dendrobium nobile Lindl on chronicunpredictable mild stress-induced depressive mice
JIANG Ning, FAN Lin-Xi, YANG Yu-Jie, LIU Xin-Min, LIN Hai-Ying, GAO Li, WANG Qiong
Preclinical Medicine Research Center/School of Pharmacy, Southwest Medical University, Luzhou 646000, China； Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China； Xinjiang Institute of Traditional Uighur Medicine, Urumqi 830049, China
To investigate whether the extract of Dendrobium nobile Lindl (DNL) has an antidepressant effect on chronic unpredictable mild stress (CUMS)-induced depressive mice, 72 BALB/c male mice were randomly divided into the control group, the CUMS model group, the extract of DNL groups (50, 100 and 200 mg/kg DNL, i.g.) and the paroxetine group (10 mg/kg, i.g.). The different doses of DNL or the paroxetine was administered orally once daily to CUMS mice for 8 weeks (containing two-week preventive medication before the modeling). The same volume of distilled water was given to the control group and the CUMS group. Except for the control group, the other mice were exposed to chronic stress for 35 days. Behavioral tests were performed by using the sucrose preference test (SPT), the novelty-suppressed feeding (NSF) test, the tail suspension test (TST), and the forced swim test (FST). The levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) were measured by the liquid chromatography-mass spectrometer (LC-MS)/MS. Compared with the control group, obvious behavioral changes were observed in the CUMS group after 5-week CUMS, including a decrease in the sucrose consumption, an increase in the latency to feeding in the NSF test and a prolongation of the immobility time in the TST. Compared with the CUMS group, the application of DNL resulted in a dose-dependent increase in sucrose consumption (P < 0.01) as paroxetine (10 mg/kg) did and a significant dose-dependent decrease in the latency to feeding in the NSF test (P < 0.05). In the TST, the application of paroxetine (10 mg/kg) and the high-dose DNL (200 mg/kg) obviously decreased the immobility time when compared with the CUMS group (P < 0.05). In the FST, compared with the CUMS group, all the groups had no significant differences in the immobility time (P > 0.05). In addition, in the hippocampus and cortex, the levels of 5-HT and DA were significantly decreased in the CUMS group compared with the control group (P < 0.05). In comparison with the CUMS group, paroxetine obviously increased the DA levels in the hippocampus and the cortex and the 5-HT level in the hippocampus (P < 0.05). DNL (50 and 200 mg/kg) significantly increased the DA level in cerebral cortex of the brain, and DNL (100 and 200 mg/kg) increased the DA level in the hippocampus. The 5-HT level in the 200 mg/kg DNL group was notably increased in both two brain regions (P < 0.05), but the 5-HT level in the 100 mg/kg DNL group was significantly increased only in the hippocampus (P<0.01). These findings indicate that the extract of DNL has an antidepressant-like effect on CUMS-induced depressive mice and its mechanism may be related to the changes in DA and 5-HT in the hippocampus and cortex.
通讯作者：王琼 E-mail: email@example.com
姜宁, 范琳犀, 杨玉洁, 刘新民, 林海英, 高莉, 王琼. 金钗石斛提取物对慢性不可预见应激模型小鼠的抗抑郁作用[J]. 生理学报 2017; 69 (2): 159-166.
JIANG Ning, FAN Lin-Xi, YANG Yu-Jie, LIU Xin-Min, LIN Hai-Ying, GAO Li, WANG Qiong. Antidepressant effects of the extract of Dendrobium nobile Lindl on chronicunpredictable mild stress-induced depressive mice. Acta Physiol Sin 2017; 69 (2): 159-166 (in Chinese with English abstract).