疏肝解郁法治疗慢性应激疗效显著。课题组前期发现疏肝解郁方药逍遥散显著改善慢性应激大鼠海马神经可塑性。BDNF是神经可塑性的重要调节因子，最新研究发现FKBP在GR的介导下，可调节BDNF的表达。因此，我们提出基于疏肝解郁治法，逍遥散可通过FKBPs/GR/BDNF信号通路调节慢性应激大鼠海马神经可塑性的假说。本研究拟建立慢性应激动物及细胞模型，观察体内外逍遥散改善神经可塑性的作用；检测其行为学及形态学指标，釆用Western Blot、RT-PCR等方法，从蛋白、mRNA水平检测逍遥散对FKBPs、GR、BDNF表达的影响；以电泳迁移率实验及以免疫共沉淀法检测相关蛋白的结合情况，双荧光素酶报告基因检测的方法探讨FKBPs对GR转录、定位的调节作用。从多个角度、多个层面论证我们的假说。本课题将进一步揭示逍遥散调节慢性应激海马神经可塑性的分子机制，为寻求防治慢性应激的新靶点提供理论和实验依据。

Xiaoyaosan Decoction has significant therapeutic effect on the chronic stress. Our team had found that Xiaoyaosan Decoction can significantly improve the hippocampal neural plasticity during the chronic stress in rats. .BDNF is an important regulator on neural plasticity. Recently study demonstrates that FKBP can regulate the expression of BDNF mediating by the GR activity. We propose the Xiaoyaosan Decoction regulates the hippocampal neural plasticity during the chronic stress through the FKBP/GR/BDNF signaling pathway..We will establish chronic stress animal and cell model, determine the behavioral and morphological data in vitro and in vivo. We will test the protein and mRNA expression of FKBPs, GR, BDNF in these models using Western Blot, RT-PCR and other methods.We will detecte the protein binding by EMSA and Co-immunoprecipitation. Dual-Luciferase Reporter Assay will tell us that FKBPs how regulate GR’s nuclear transcription and the effect of Xiaoyaosan Decoction..By this project, we will confirm our hypothesis.We will clarify the molecular mechanism on the regulation of hippocampal neuralplasticity induced by Xiaoyaosan Decoction during the chronic stress. We will find some novel targets for the treatment of chronic stress，and provide the direct evidences.

疏肝解郁法治疗慢性应激疗效显著。课题组前期发现疏肝解郁方药逍遥散显著改善慢性应激大鼠海马神经可塑性。BDNF是神经可塑性的重要调节因子，最新研究发现FKBP在GR的介导下，可调节BDNF的表达。因此，我们提出基于疏肝解郁治法，逍遥散可通过FKBPs/GR/BDNF信号通路调节慢性应激大鼠海马神经可塑性的假说。本研究通过建立慢性应激动物及细胞模型，观察体内外逍遥散改善神经可塑性的作用；检测其行为学及形态学指标，釆用Western Blot、RT-PCR等方法，从蛋白、mRNA水平检测逍遥散对FKBPs、GR、BDNF表达的影响；以电泳迁移率实验及以免疫共沉淀法检测相关蛋白的结合情况，双荧光素酶报告基因检测的方法探讨FKBPs对GR转录、定位的调节作用。通过本研究发现疏肝解郁方药逍遥散通过调控慢性应激损伤大鼠海马神经元细胞内FKBP表达，增强GR入核活性，上调GR靶基因BDNF表达，改善海马神经可塑性，从而发挥抗应激损伤的效果。研究结果从多个角度、多个层面证实了课题组提出的科学假说。部分揭示了逍遥散调节慢性应激海马神经可塑性的分子机制，为寻求防治慢性应激的新靶点提供了理论和实验依据。