缝隙连接功能变化对抑郁模型大鼠海马神经重塑的影响及中药干预研究

Depression is a common affective disorder disease with an increasing incidence year by year but the pathogenesis is still unknown. Recent studies suggest that the decline of hippocampal neuronal plasticity is highly related to depression. Gap junctions play an important role in the normal functions of neurons as well as in the maintenance of the internal and external environment stability of nerve cells. Gap junctions are also involved in nerve regeneration and functional remodeling, and its dysfunction will induce core symptoms of depression. Based on modern medical understanding of the pathogenesis of depression, the purpose of this project is to prepare stressing rat model of depression via chronic stimulation and intervene with traditional Chinese medicine. This project is also going to clarify the gap junction function of the changing pattern of hippocampal nerve remodeling, which will be mainly achieved in two directions. From the microscopic and submicroscopic level, observation of the neuronal cell morphology, structure and number of changes are to be performed, while from the molecular level, analysis of the hippocampus of the gap junction protein, connexin phosphorylation and gap junction binding protein expression changes also lead to the goal. The study contributes to understanding the pathogenesis of depression, providing theoretical and experimental basis to traditional Chinese medicine treatment of depression, and to laying the foundation for new drug development of Chinese medicine treatment for clinical use.

抑郁症是一种常见的情感性精神障碍疾病，其发病率逐年上升但发病机制不明。近年来的研究提示抑郁症与海马神经可塑性下降密切相关。缝隙连接对维持神经细胞内外环境稳定及神经元正常功能中起重要作用，参与神经再生与功能重塑，其功能障碍会诱发抑郁症的核心症状。本课题旨结合现代医学对抑郁症发病机理的认识，采用慢性应激方法制备抑郁模型大鼠并用中药进行干预，从显微和亚显微水平观察海马神经细胞形态结构和数量的改变，从分子水平分析海马区缝隙连接蛋白、缝隙连接蛋白磷酸化和缝隙连接相关结合蛋白的表达变化，以阐明缝隙连接功能变化模式对海马神经重塑的影响。该研究有助于认识抑郁症的发病机制，为临床采用中药复方治疗抑郁症提供理论和实验依据，为开发治疗抑郁症的中药新药奠定基础。