基于Notch与JAK／STAT信号串话研究卒中后应激大鼠神经重塑及益肾调气中药的干预机制

卒中后抑郁（PSD）是脑卒中后常见的精神障碍，海马体积缩小是其重要的病理特征。神经干细胞增殖分化障碍是海马体积改变的原因之一，多个信号转导通路参与其中，其相互之间的“串话”决定了海马神经干细胞的命运。本项目拟围绕海马重塑过程中的Notch1与JAK2／STAT3信号通路，在体外应用Notch1与STAT3信号阻断剂，以明确二者之间的“串话”对海马神经干细胞增殖分化的影响。并采用病理观察、免疫组化、蛋白印迹、RT-PCR等方法，研究PSD大鼠造模后2、4、6周海马结构及Notch1、Jagged1、 Hesl、Hes5、JAK2、STAT3、p-JAK2、p-STAT3等信号分子的变化，以益肾调气活血中药颐脑解郁方进行干预，旨在探讨Notch1与JAK2／STAT3信号的“串话”在PSD海马神经重塑过程中的作用及益肾调气活血中药的干预机制。本项目可有益补充PSD发病机制和中医神志病学理论。

Post stroke depression (PSD) is a common mental disorder after stroke, one of important pathological features is shrunk hippocampal volume due to impairment of neural stem cell proliferation and differentiation, in which a lot of signal transduction pathways involved. "Crosstalk" between the signal transduction pathways determines the hippocampal neural stem cell fate. This project is proposed to focus on hippocampal remodeling invovling Notch1 and JAK2 / STAT3 signaling pathways. Notch1 and STAT3 signal blocking agent are used to reveal that how “crosstalk” between the two signal pathways effect hippocampal neural stem cell proliferation and differentiation in vitro. And the pathological observation, immunohistochemistry, Western blotting and RT-PCR method are taken in animal experiment. Hippocampal structure and changes of Notch1, Jagged1, Hes1, Hes5, JAK2, STAT3, p-jak2, p-STAT3 and signal molecular are observed 2nd, 4th, 6th week after PSD model rats are duplicated. Chinese herb with tonifying kidney and regulating qi and promoting blood circulation-YiNaoJieYu formula are administrated. The purpose of this project is to clarify the role of “crosstalk” between Notch1 and JAK2 / STAT3 signal pathways in the development of hippocampal neural remodeling of PSD and underlying mechanism of YiNaoJieYu formula. This project can be benefit to PSD pathogenesis and TCM theory of mental diseases.