基于SGK1研究抑郁症海马隔颞轴神经元再生障碍及中药干预

抑郁症是危害人类健康的重大疾患，海马神经元再生障碍为其重要发病机制。隔颞轴系贯穿腹侧、背侧海马的纵向长轴，具有调控腹侧海马情绪处理和背侧海马学习记忆的功能。海马神经元再生主要分布于隔颞轴，然而其机制尚不明确，国内外尚无报道。血清和糖皮质激素诱导的蛋白激酶1（SGK1）广泛分布于海马隔颞轴并可调控海马神经元再生。本课题组前期临床研究发现“疏肝解郁，活络安神”立法的百事乐胶囊对“肝郁气滞”型抑郁患者疗效显著；实验研究表明其能下调抑郁模型大鼠海马SGK1的表达，并促进齿状回和CA3区神经元再生。本研究拟在前期研究基础上，通过在体与体外研究，运用行为药理学和流式细胞及荧光可视等技术，研究皮质醇（COR）持续升高，SGK1上调，介导海马隔颞轴神经再生障碍，进而诱发抑郁症的分子机制，阐明以“疏肝解郁、活络安神”治法的百事乐胶囊调节隔颞轴海马神经元再生的作用机理，为中药防治抑郁的研究提供新的思路与靶点。

Depression is a major health problem, its main mechanism is hippocampal neurogenesis damage. The vertical long axis of the dorsal and ventral hippocampus is connected named septo-temporal axis, and it could regulate learn, memory and emotional processing.The hippocampal neurogenesis is distributed along the septo-temporal axis. However, its mechanism is still unknown, there is on report about it. Serum and glucocorticoid-induced protein kinase1 (SGK1) can regulate hippocampal neurogenesis, and distributed along the septo-temporal axis. Our previous work have demonstrated that the Baishile Capsule based on “shuganjieyu, huoluoanshen” could treat depression patients in the state of “ganyuqizhi” with significant efficiency. Also, it could decreased the expression of SGK1 in hippocampal, and promote hippocampal neurogenesis in DG and CA3. Upon these evidences and our previous results, in present study, we plan to investigate the molecular mechanisms of SGK1 on neurogenesis in septo-temporal axis with high cortisol at whole animal level and cell level, with the application of multiple research approaches including behavioral pharmacology, flow cytometry and fluorescence visualization technology, to clarify the mechanism and target gene of Baishile Capsule with “shuganjieyu, huoluoanshen” regulate hippocampus neurogenesis. In order to provide new idea and target for antidepressant signaling pathway research of Traditional Chinese medicine.