Wang Chunye, Guo Jianyou, Guo Rongjuan
Dongfang Hospital Beijing University of Chinese Medicine, 100078, Beijing, China.
CAS, Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 100101, Beijing, China.
BMC Complement Altern Med. 2017 Jan 24;17(1):73. doi: 10.1186/s12906-016-1543-9.
Depression is a mental disorder characterized by a pervasive low mood and loss of pleasure or interest in usual activities, and often results in cognitive dysfunction. The disturbance of cognitive processes associated with depression, especially the impairment of learning and memory, exacerbates illness and increases recurrence of depression. XingPiJieYu (XPJY) is one of the most widely clinical formulas of traditional Chinese medicine (TCM) and can improve the symptoms of depression, including learning and memory. However, its regulatory effects haven't been comprehensively studied so far. Recently, some animal tests have indicated that the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element-binding protein (CREB)-brain derived neurotrophic factor (BDNF) signaling pathway in hippocampus is closely related to depression and the pathogenesis of cognitive function impairments. The present study was performed to investigate the effect and mechanism of XPJY on depression and learning and memory in animal model.
The rat model of depression was established by chronic unpredictable stress (CUS) for 21 days. The rats were randomly divided into six groups: control group, CUS group, CUS + XPJY (1.4 g/kg, 0.7 g/kg and 0.35 g/kg) groups, and CUS + sertraline (10 mg/kg) group. The sucrose preference, open field exploration and Morris water maze (MWM) were tested. The expression of cAMP, CREB, PKA and BDNF protein in hippocampus was examined with Elisa and Western Blot. The mRNA level of CREB and BDNF in hippocampus was measured with PCR.
The results demonstrated that rats subjected to CUS exhibited decreases in sucrose preference, total ambulation, percentage of central ambulation, rearing in the open field test and spatial performance in the MWM. CUS reduced the expression of cAMP, PKA, CREB and BDNF in hippocampus of model rats. These effects could be reversed by XPJY.
The results indicated that XPJY can improve depression and related learning and memory and the effect of XPJY is partly exerted through the cAMP-PKA-CREB-BDNF signaling pathway.
抑郁症是一种以普遍情绪低落以及对日常活动丧失愉悦感或兴趣为特征的精神障碍，常导致认知功能障碍。与抑郁症相关的认知过程紊乱，尤其是学习和记忆受损，会加重病情并增加抑郁症的复发率。醒脾解郁（XPJY）是中医临床应用最为广泛的方剂之一，能够改善抑郁症症状，包括学习和记忆。然而，其调节作用至今尚未得到全面研究。最近，一些动物实验表明，海马体中的环磷酸腺苷（cAMP）-蛋白激酶A（PKA）-cAMP反应元件结合蛋白（CREB）-脑源性神经营养因子（BDNF）信号通路与抑郁症及认知功能障碍的发病机制密切相关。本研究旨在探讨醒脾解郁方对动物模型抑郁症及学习记忆的影响及其机制。
通过慢性不可预测应激（CUS）建立大鼠抑郁症模型，持续21天。将大鼠随机分为六组：对照组、CUS组、CUS + XPJY（1.4 g/kg、0.7 g/kg和0.35 g/kg）组以及CUS + 舍曲林（10 mg/kg）组。进行蔗糖偏好、旷场探索和莫里斯水迷宫（MWM）测试。采用酶联免疫吸附测定法（ELISA）和蛋白质免疫印迹法检测海马体中cAMP、CREB、PKA和BDNF蛋白的表达。用聚合酶链反应（PCR）检测海马体中CREB和BDNF的mRNA水平。
结果表明，遭受CUS的大鼠在旷场试验中的蔗糖偏好、总活动量、中央活动百分比、直立次数以及在MWM中的空间表现均降低。CUS降低了模型大鼠海马体中cAMP、PKA、CREB和BDNF的表达。醒脾解郁方能逆转这些作用。
结果表明，醒脾解郁方可以改善抑郁症及相关学习记忆，其作用部分是通过cAMP-PKA-CREB-BDNF信号通路发挥的。
Zotero 插件
