电针治疗抑郁有效且副作用少，但作用机制仍不明确。本课题组临床研究表明，针药结合可快速起效，fMRI研究表明电针靶向作用的脑区之一为海马；动物实验与临床观察一致，且电针能逆转抑郁状态的海马突触结构可塑性变化；蛋白组学研究发现其分子机制与突触后膜AMPA受体（AMPAR）特异性去乙酰化酶SIRT2的活性相关。因此我们提出假说：电针通过影响海马SIRT2活性调控突触后膜AMPAR乙酰化水平，减少受体蛋白降解，影响突触可塑性，促进药物快速起效。基于假说，本研究拟对抑郁大鼠进行电针、针药结合干预，基于行为学指标评估干预效果；运用电生理及免疫电镜技术，观察海马突触可塑性的改变；并检测能量通路改变及SIRT2酶活性的变化；运用免疫沉淀技术、免疫荧光技术和免疫印迹法检测SIRT2与AMPAR相互作用的改变；最后，对SIRT2敲除动物进行干预，完成验证。为电针治疗抑郁症提供新的依据。

Electroacupuncture therapy provides a less adverse treatment for depression. However, its mechanism remains largely unknown. Our previous RCT study shows that combination treatment of electroacupuncture (at GV20 and GV29) and paroxetine (a widely used SSRI) improves depressive symptoms within short period of time (less than 1 week). fMRI study shows that one of its targeting brain area is hippocampus. Later animal experiment remains consistent. Further ultrastructure study shows significant hippocampal postsynaptic density change, and proteomics study reveals that mechanism of electroacupuncture effect is tightly connected to hippocampal SIRT2-regulating post-translational acetylation of AMPAR. Therefore, based on our previous studies, we hypothesize that electroacupuncture works by improving AMPAR density related synaptic plasticity in hippocampus, through changing the enzymatic activity of SIRT2. Firstly， evaluate the efficacy of electroacupuncture, hippocampal synaptic plasticity change, its impact on metabolism, SIRT2 activity and SIRT2-AMPAR interaction using ethological tests, electrophysiology tests and immunoelectron microscopy, enzymatic activity testing and immunoprecipitation, immunoblotting and immunofluorescent assays. Then we are gonging to perform electroacupuncture on SIRT2 knockout mice to further prove the hypothesis.