百合地黄汤通过磷酸酶SHP2改善焦虑性抑郁症BLA－vHPC神经通路损伤的机制研究

情志疾病的发生通常是多个脑区联动损伤的结果。基底外侧杏仁核－腹侧海马（BLA－vHPC）神经通路是杏仁核与海马共同调节情绪行为的神经基础，其结构功能的损伤与焦虑性抑郁症病程演进息息相关。研究表明，酪氨酸磷酸酶SHP2在过度活化状态下能经由AMPA受体致突触重塑障碍，而突触重塑障碍是BLA－vHPC结构损伤、功能紊乱的核心因素。前期证实，焦虑性抑郁症状态下SHP2酶活性增加，突触可塑性损伤。百合地黄汤基于焦虑性抑郁症“阴虚内热”病机进行治疗，效果显著，能恢复神经突触可塑性，保护杏仁核-海马组织。我们推测：百合地黄汤通过调控SHP2改善BLA－vHPC神经通路损伤发挥抗焦虑抑郁功效。本研究拟整合神经影像学、神经生物学、分子生物学等技术方法，从整体、组织、细胞和分子水平明确百合地黄汤治疗焦虑性抑郁症的作用环节与关键靶点，阐释“滋阴清热、宁心安神”治法的科学内涵，为情志病的临床防治提供理论依据。

Emotional diseases are usually the result of linkage damage to multiple brain regions. The basolateral amygdala-ventral hippocampus (BLA-vHPC) neural pathway is the neural basis for the amygdala and hippocampus to regulate emotional behavior. The damage of its structure and function is closely related to the course of anxious depression. Studies have shown that tyrosine phosphatase SHP2 can cause synaptic remodeling disorder via AMPA receptors under over-activated state, and synaptic remodeling disorder is the core factor of BLA-vHPC structural damage and dysfunction. Previous studies have shown that SHP2 enzyme activity increases and synaptic plasticity is impaired in anxious depression. Baihe Dihuang decoction is based on the pathogenesis of anxious depression "Yin deficiency and internal heat", and the effect is remarkable. It can restore neurosynaptic plasticity and protect the amygdala-hippocampus tissue. We deduced that Baihe Dihuang decoction exerts anti-anxiety and depression effects by regulating SHP2 to improve BLA-vHPC nerve pathway damage. This study intends to integrate neuroimaging, neurobiology, molecular biology and other technical methods to clarify the role and key targets of Baihe Dihuang decoction in the treatment of anxious depression from the overall, tissue, cellular and molecular levels, and to explain the scientific connotation of "Nourishing Yin, Clearing Heat, Calming the Heart and Soothing the Mind", and provide a theoretical basis for the clinical prevention and treatment of emotional diseases.