Xiaoyaosan exerts anxiolytic-like effects by down-regulating the TNF-α/JAK2-STAT3 pathway in the rat hippocampus.
Xiaoyaosan exerts anxiolytic-like effects by down-regulating the TNF-α/JAK2-STAT3 pathway in the rat hippocampus.
复制标题
逍遥散通过下调大鼠海马 TNF-α/JAK2-STAT3 通路发挥抗焦虑样作用
DOI：
10.1038/s41598-017-00496-y
复制
发表时间：
2017-03-23
影响因子：
4.6
通讯作者：
Chen JX
中科院分区：
文献类型：
--
作者：
Li XJ;Ma QY;Jiang YM;Bai XH;Yan ZY;Liu Q;Pan QX;Liu YY;Chen JX
虽然中药消药散具有抗焦虑作用，但其作用机制尚不明确。细胞因子肿瘤坏死因子-α (TNF-α)及其密切相关的janus kinase 2 (JAK2)-信号转导和转录激活因子（STAT3）信号通路调节大脑的神经炎症反应，从而参与焦虑的发生。我们的目的是研究消药散的抗焦虑样作用是否与海马中TNF-α/JAK2-STAT3通路有关。在慢性固定应激（CIS）诱导的焦虑大鼠模型中，我们研究了消药散对升高+迷宫试验、开放场试验和新奇性抑制喂养试验中表现出的行为以及海马神经元损伤和TNF-α/JAK2-STAT3通路变化的影响。消药散对cis诱导的焦虑具有抗焦虑样作用，可显著减轻焦虑样行为，减轻海马神经元损伤，逆转海马中TNF-α/JAK2- stat3通路的激活，其作用与JAK2拮抗剂AG490相似。而消药散和AG490未能有效调节凋亡相关因子Bax和Caspase-3。这些结果表明，消药散通过下调大鼠海马中TNF-α/JAK2-STAT3通路来减轻应激性焦虑行为。
Although the anxiolytic-like effects of Xiaoyaosan, a Chinese herbal formula, have been described in many previous studies, its underlying mechanism remains undefined. The cytokine tumour necrosis factor-α (TNF-α) and its closely associated janus kinase 2 (JAK2)-signal transducer and activator of transcription (STAT3) signalling pathway regulate the neuro-inflammatory response in the brain, thus participating in the development of anxiety. Our purpose was to investigate whether the anxiolytic-like effects of Xiaoyaosan are related to the TNF-α/JAK2-STAT3 pathway in the hippocampus. We examined the effects of Xiaoyaosan on behaviours exhibited in the elevated plus maze test, open field test and novelty-suppressed feeding test as well as hippocampal neuron damage and changes in the TNF-α/JAK2-STAT3 pathway in a rat model of chronic immobilization stress (CIS)-induced anxiety. Xiaoyaosan exerts anxiolytic-like effects on CIS-induced anxiety, with a significant alleviation of anxiety-like behaviours, an attenuation of hippocampal neuron damage, and a reversal of the activation of the TNF-α/JAK2-STAT3 pathway in the hippocampus that are similar to the effects of the JAK2 antagonist AG490. However, Xiaoyaosan and AG490 failed to effectively regulate apoptosis-related factors, including Bax and Caspase-3. These results suggest that Xiaoyaosan attenuates stress-induced anxiety behaviours by down-regulating the TNF-α/JAK2-STAT3 pathway in the rat hippocampus.