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黄连解毒汤提取物通过BDNF-TrkB-CREB通路改善慢性不可预测应激大鼠的抑郁样行为

Huanglian-Jie-Du-Tang Extract Ameliorates Depression-Like Behaviors through BDNF-TrkB-CREB Pathway in Rats with Chronic Unpredictable Stress.

作者信息

Ye Yi-Lu, Zhong Kai, Liu Dan-Dan, Xu Jing, Pan Bei-Bei, Li Xiang, Yu Yue-Ping, Zhang Qi

机构信息

Basic Medicine Department, Hangzhou Medical College, Hangzhou 310053, China.

The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.

出版信息

Evid Based Complement Alternat Med. 2017;2017:7903918. doi: 10.1155/2017/7903918. Epub 2017 Jun 14.

DOI:10.1155/2017/7903918
PMID:28694833
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5488320/
Abstract

Neuroinflammation is considered as one of the common pathogeneses of depression. Huanglian-Jie-Du-Tang (HJDT) is a traditional Chinese herbal formula. The present study investigates the antidepressant-like effect of HJDT and its possible mechanism in rats. Rats were given HJDT (2, 4, and 8 g/kg, intragastrically), paroxetine (1.8 mg/kg, intragastrically), or an equivalent volume of saline for 42 days. The depression-related behaviors, including sucrose preference test (SPT), open field test (OFT), novel objective recognition task (NORT), and forced swimming test (FST), were detected. 5-Hydroxytryptamine (5-HT) and dopamine (DA) contents, microglial activation, proinflammatory cytokines, and brain derived neurotrophic factor (BDNF), tropomyosin receptor kinases B (TrkB), and cAMP-responsive element binding protein (CREB) expression were investigated. The results indicated HJDT (2 and 4 g/kg) dramatically ameliorated the depression-like behaviors. Also HJDT decreased the number of microglia and the proinflammatory cytokines in hippocampus. Western-blotting analysis displayed HJDT upregulated BDNF, TrkB, and pCREB/CREB expression in hippocampus. Particularly, pCREB DNA activity enhanced with HJDT treatment in hippocampus. But there was no difference in the 5-HT and DA contents with HJDT treatment. In conclusion, it was supposed that HJDT might be a potential Chinese medicine decoction for treating or alleviating complex symptoms of depression through BDNF-TrkB-CREB pathway.

摘要

神经炎症被认为是抑郁症常见的发病机制之一。黄连解毒汤(HJDT)是一种传统的中药配方。本研究探讨了黄连解毒汤对大鼠的抗抑郁样作用及其可能的机制。给大鼠灌胃给予黄连解毒汤(2、4和8 g/kg)、帕罗西汀(1.8 mg/kg)或等体积的生理盐水,持续42天。检测与抑郁相关的行为,包括蔗糖偏好试验(SPT)、旷场试验(OFT)、新物体识别任务(NORT)和强迫游泳试验(FST)。研究了5-羟色胺(5-HT)和多巴胺(DA)含量、小胶质细胞活化、促炎细胞因子以及脑源性神经营养因子(BDNF)、原肌球蛋白受体激酶B(TrkB)和环磷酸腺苷反应元件结合蛋白(CREB)的表达。结果表明,黄连解毒汤(2和4 g/kg)显著改善了抑郁样行为。黄连解毒汤还减少了海马中小胶质细胞的数量和促炎细胞因子的含量。蛋白质印迹分析显示,黄连解毒汤上调了海马中BDNF、TrkB和pCREB/CREB的表达。特别是,黄连解毒汤治疗后海马中pCREB的DNA活性增强。但黄连解毒汤治疗后5-HT和DA含量没有差异。总之,推测黄连解毒汤可能是一种通过BDNF-TrkB-CREB途径治疗或缓解抑郁症复杂症状的潜在中药汤剂。

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