开心散是抗抑郁经典方剂，前人研究已证实其明确的抗抑郁效用。申请者发现其不仅可调控神经递质、还可调控并增益神经营养因子发挥抗抑郁作用。近年来，国内外研究证实，抑郁症与肠道微生态紊乱密切相关。压力应激导致肠道菌群变化，损伤肠道屏障，诱发中枢神经炎症，加剧压力应激，构成系统回路，加剧抑郁程度。我们拟基于此回路，构建动物与细胞模型，深入探索开心散抗抑郁机制，拟开展以下工作：（1）通过压力激素与相应受体表达测定，探索开心散调控压力应激系统的效用机制；（2）采用高通量基因测序与Ussing Chamber等技术，阐述开心散对肠道菌群结构与肠道屏障功能的调控机制；（3）通过炎性因子、神经递质、神经营养因子与相关调控酶测定，揭示开心散调控中枢神经炎症系统的效用机制；（4）构建细胞模型深入机制研究。从而系统阐释开心散调节压力应激-肠道微生态-中枢神经炎症系统抗抑郁的作用机制，为开发抑郁症治疗药物提供科学依据

As a classical TCM formula for treating major depression disorder, the clinical efficacy of Kai-Xin-San (KXS) had been confirmed and the mechasim was revealed by monitoring neurotransmitters and potentiating neurotrophic factors. Now, it has been found that disturbance of intestinal microecology should be included in pathology of depression. In details, stress induces changes of intestinal microbiota and injury of intestinal barrier, which leads to neuronal inflammaiton of central nervous system and excitation of HPA axis. Under this circumstance, depression is caused. Here, the anti-depression machanism of KXS will be further elucidated on depression animal and cell models via this newly discovered pathological mechanism. Firstly, the effect of KXS on stress system will be explored by determining the expressions of stress hormones and related receptors. Secondly, via technologies of highflux gene sequencing and ussing chamber, the effect of KXS on intetinal microbiota composition and intestinal barrier function will be elucidated. Thirdly, the effect of KXS on neuronal inflammaiton of central nervous system will be explored by determining the expressions of inflammantory factors, neurotranismitters, neurotrophic factors and related monitoring enzyemes. Finally, the action machanism of KXS on these revealed targets will be further explored on cell models. Based on these researches, we hope to elucide the anti-depression mechansim of KXS via monitoring stress-intestinal microecology-central neuronal inflammation circuit, which will be helpful for supplying more scientific evidences for development of anti-depressant.