Jiao Haiyan, Yan Zhiyi, Ma Qingyu, Li Xiaojuan, Jiang Youming, Liu Yueyun, Chen Jiaxu
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China,
Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, Guangdong, China,
Neuropsychiatr Dis Treat. 2018 Dec 18;15:21-31. doi: 10.2147/NDT.S185295. eCollection 2019.
Tryptophan metabolism has always been considered to play a vital role in mental disorder diseases, and how traditional Chinese formula Xiaoyaosan regulates the tryptophan metabolism is a complement to the pathogenesis of depression. This study established a depression rat model by the chronic immobilization stress (CIS) method and observed the change in tryptophan metabolism in hippocampus and the effects of Xiaoyaosan.
Forty-eight male Sprague Dawley (SD) rats were randomly divided into the following four groups: control group, CIS group, Xiaoyaosan group, and fluoxetine group. The depression model was established by the 21-day CIS. The food intake and body weight were recorded, and the sucrose preference test (SPT), novelty suppressed feeding (NSF) test and open field test (OFT) were also used to evaluate the model. Then, the contents of tryptophan and 5-hydroxytryptamine (5-HT) in hippocampus were detected by the ELISA method, and the expression levels of tryptophan hydrogenase 2 (TPH2) and indoleamine 2,3-dioxygenase 1 (IDO1) in hippocampus were determined by quantitative reverse transcriptase polymerase chain reaction reaction (qRT-PCR) and Western blot methods.
The behavioral data showed a significant difference between the model group and the normal group. The 5-HT content in the hippocampi of CIS rats was significantly reduced, whereas the tryptophan content in the hippocampi of model rats was significantly increased. The TPH2 level in hippocampus of the model group was significantly decreased, and the IDO1 level was significantly increased. Xiaoyaosan and fluoxetine could significantly reverse these changes and had obvious curative effects.
The abnormal tryptophan metabolism existed in the hippocampi of chronic stress-depressed rats, which was closely related to the pathogenesis of depression. Xiaoyaosan could improve the tryptophan metabolism by regulating the expression levels of TPH2 and IDO1, thus exerting an antidepressant-like effect.
色氨酸代谢一直被认为在精神障碍疾病中起着至关重要的作用，而中药方剂逍遥散如何调节色氨酸代谢是对抑郁症发病机制的补充。本研究采用慢性束缚应激（CIS）法建立抑郁症大鼠模型，观察海马中色氨酸代谢的变化及逍遥散的作用。
将48只雄性Sprague Dawley（SD）大鼠随机分为以下四组：对照组、CIS组、逍遥散组和氟西汀组。通过21天的CIS建立抑郁症模型。记录食物摄入量和体重，并采用蔗糖偏好试验（SPT）、新奇抑制摄食（NSF）试验和旷场试验（OFT）评估模型。然后，采用酶联免疫吸附测定（ELISA）法检测海马中色氨酸和5-羟色胺（5-HT）的含量，采用定量逆转录聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法检测海马中色氨酸羟化酶2（TPH2）和吲哚胺2,3-双加氧酶1（IDO1）的表达水平。
行为学数据显示模型组与正常组之间存在显著差异。CIS大鼠海马中的5-HT含量显著降低，而模型大鼠海马中的色氨酸含量显著增加。模型组海马中的TPH2水平显著降低，IDO1水平显著升高。逍遥散和氟西汀可显著逆转这些变化，具有明显的治疗效果。
慢性应激抑郁大鼠海马中存在色氨酸代谢异常，这与抑郁症的发病机制密切相关。逍遥散可通过调节TPH2和IDO1的表达水平改善色氨酸代谢，从而发挥抗抑郁样作用。
