基于杏仁核CRF1受体信号通路的逍遥散改善慢性应激焦虑证的作用机制

As increasingly society competition, incidence of depression, anxiety and other emotional disorders induced by stress is increasing year by year.Chinese medicine holds that pathological mechanism of anxiety induced by chronic stress is associated with unbalance of liver.Xiaoyao powder has significant clinical effects, but the mechanism needs to be clarified. Amygdala plays an important role in the occurrence of anxiety. CRF1 receptor and post-receptor signaling pathway cAMP / pCREB / BDNF mediates chronic stress injury mechanism.Along the amygdala, CRF1 receptor pathway to explore the mechanism of Xiaoyaosan is feasible.This will help to clarify the mechanism of xiaoyao powder.Based on preliminary studies,this project will use chronic restraint stress model and amygdala microinjection technology to observe the effect of xiaoyao powder on anxiety-like behavior and CRF1 receptor pathway.All of this is to clarify part of mechanism of xiaoyao powder reduced anxiety-like behavior induced by chronic restraint stress.

随着社会竞争的日益激烈，应激导致的抑郁、焦虑等情绪功能紊乱发病率呈逐年上升趋势。中医认为慢性应激焦虑证的病理机制与肝失疏泄、气郁化火密切相关。逍遥散是郁证代表方，临床作用显著，然而其机制研究有待深入。杏仁核在焦虑的发生中起重要作用；CRF1受体及受体后信号通路cAMP/pCREB/BDNF介导了慢性应激损伤的作用机制。沿着杏仁核、CRF1受体通路探讨逍遥散的作用机制具有可行性，有助于明确逍遥散改善慢性应激损伤的作用机制。本课题在前期研究基础上，拟复制慢性束缚应激焦虑证大鼠模型，结合杏仁核内微量注射技术，从行为学、分子生物学水平观察逍遥散对模型焦虑样行为、CRF1受体及受体后信号通路cAMP/pCREB/BDNF的影响，以期部分阐明逍遥散改善慢性应激焦虑证的作用机制；并为以CRF1受体为靶点的新药研发提供可靠的实验依据。

应激导致的抑郁、焦虑等情绪功能紊乱发病率呈逐年上升趋势。中医认为慢性应激焦虑证的病理机制与肝失疏泄、气郁化火密切相关。逍遥散是郁证代表方，临床作用显著，然而其机制研究有待深入。杏仁核在焦虑的发生中起重要作用；CRF1 受体及受体后信号通路cAMP/pCREB/BDNF 介导了慢性应激损伤的作用机制。本课题在前期研究基础上，复制慢性束缚应激焦虑证大鼠模型，结合杏仁核内微量注射技术，从行为学、分子生物学水平观察逍遥散对模型焦虑样行为、CRF1 受体及受体后信号通路cAMP/pCREB/BDNF 的影响。实验结果显示：①逍遥散均能够在一定程度上改善焦虑样行为。②杏仁核微量注射CRF1受体激动剂后，其行为学效应能够部分模拟慢性应激状态，提示CRF1受体作为应激反应的重要因子参与了杏仁核调节焦虑的反应，逍遥散通过影响杏仁核CRF1受体来发挥调节焦虑的作用。③通过检测各组大鼠杏仁核上CRF1受体及信号通路的变化，进一步明确了逍遥散改善慢性应激焦虑证的部分作用机制是通过调控杏仁核CRF1受体信号通路来发挥作用。