抑郁症是情志致郁临床表现形式之一。基于临床报道和本组前期发现：抑郁状态下机体呈现神经内分泌调控因子、促炎性细胞因子与葡萄糖和脂质等内源性物质稳态失衡，本项目认为慢性应激导致心脑情志抑郁，继而对主宰和协调肝肾功能失控，引发内源性物质紊乱，提出下丘脑内源性物质调控失衡是情志致郁重要病机的假说。本项目继续研究慢性应激抑郁症大鼠下丘脑内源性物质调控信号与因子异常(CRF系统信号亢进、NLRP3炎性小体与炎性细胞因子异常、胰岛素和瘦素信号转导通路障碍）及相互间调控失衡在内源性物质稳态破坏中所起的重要作用；并从心脑、肝、肾论治，研究解郁化痰半夏厚朴汤和黄连温胆汤、疏肝解郁柴胡疏肝散、温肾壮阳金匮肾气丸对各病理环节的逆转作用及整合调控机制。揭示慢性应激引发心脑-肝-肾脏腑功能异常与抑郁行为的关联，为推进其转化医学研究提供理论和实验基础；对方剂作用机理进一步的阐述将佐以科学诠释情志致郁并指导中医有效治疗。

Depression is one of clinical manifestations of psychogenic emotion causing Depression/Yu. Clinical studies and our previous experimental findings show that chronic stress exposure developed the unbalance of endogenous substances including neuroendocrine regulators, inflammatory cytokines and glucose and lipids. In this project, we consider that chronic stress cause emotional injury in Heart and Brain, followed by the loss of its domination and coordination of Liver and Kidney function, leading to disorders of body endogenous substances. Therefore, this project put forward the hypothesis that the steady-state destruction of endogenous substance regulation in hypothalamus may be important pathology process of psychogenic emotion causing Depression/Yu. To test this hypothesis, this project will continue to explore that disorders of hypothalamus signaling and factor for the regulation of endogenous substances (hyperactivity of CRF system signaling, activation of the NLRP3 inflammasome with inflammatory cytokine elevation, impairment of insulin and leptin signal transduction pathway) and their adjustments play the important roles in the steady-state destruction of endogenous substances in depression model of rats exposed to chronic mild stress. Moreover, this project will investigate the reversal effects and integration mechanisms of effective Chinese prescriptions relieving Depression and eliminating phlegm (Banxia Houpo decoction and Huanglian Wendan decoction), discharging Liver and relieving Yu on the pathological process (Chaihu Jieyu San), and warming Kidney and strengthening Yang (Jinkui shengqi Wan) in this animal model according to Heart and Brain-Liver-Kidney treatment in traditional Chinese medicine (TCM) theory. These results from this project will reveal the link between Heart and Brain-Liver-Kidney-related dysfunction as well as depressive behaviors in rats caused by chronic stress,and provide theoretical and experimental evidences for the promotion of the translational medicine/research. On the other hand, this project will elaborate the mechanisms of Chinese prescriptions relieving Depression and eliminating phlegm, discharging Liver and relieving Yu and warming Kidney and strengthening Yang, which will be helpful in scientically interpreting psychogenic emotion causing Depression/Yu, as well as guiding for effective clinical practice in the prevention and treatment of depression.