基于“谷氨酸-NMDA通路”介导钙超载致大鼠抑郁机制及电针的干预作用

The antidepressant effect of acupuncture has been confirmed long time ago, while the mechanism has not been clearly elucidated yet. Our previous studies have found that hippocampal astrocytes (AST) structure injury and function obstacle is one of the most important pathophysiological mechanisms of depression induced by chronic stress, while acupuncture can effectively repair the injury and obstacle of AST, but the internal molecular mechanism is unclear. In recent years, a few studies have found that stress can increase the hippocampus glutamate level significantly, promote excessive activation of NMDA receptors. As we know, excessive activation of NMDA receptors can promote cell calcium overload, leading to cell apoptosis. But the relationship between the two hasn’t reported. For this reason, in this study we would observe the glutamate content in hippocampus, Ca2+ level in AST, and protein expression and gene transcription of NR2A and NR2B. In this way to draw the conclusion: ① Chronic stress can promote excessive activation of the Glutamate-NMDA pathway, further to promote cell calcium overload of AST which can finally to induce depression of rats. ②Electro-acupuncture Siguan points can effectively to suppress the excessive activation of the Glutamate-NMDA pathway and avoid the astrocyts apoptosis. The success of this study can provide strong evidence for acupuncture clinic on depression.

针刺抗抑郁安全、有效，但作用机制迄今未清楚阐明。我们前期研究发现海马星形胶质细胞（AST）结构损伤和功能障碍是慢性应激致抑郁的重要机制，而电针可以有效修复AST的上述损伤进而发挥抗抑郁作用，但内在分子机制不明。近年来的研究发现应激能够使海马谷氨酸水平明显升高，促进NMDA受体过度激活。已知NMDA受体激活可以促进细胞钙超载，导致细胞凋亡。但对上述二者之间的相关性研究未见报道。基于此，本研究对慢性应激致抑郁大鼠海马谷氨酸含量、AST 胞质内Ca2+水平、NMDA受体关键蛋白NR2A、NR2B 基因转录及蛋白表达情况以及电针四关穴对其的调节作用进行观察，拟得出如下结论：①慢性应激促大鼠海马谷氨酸-NMDA通路过度激活、AST钙超载，进而诱发AST凋亡导致抑郁；②电针可以有效抑制谷氨酸-NMDA通路过度激活，抑制AST凋亡而抗抑郁。本研究的顺利实现将为针刺抗抑郁临床应用提供有力的实验室依据。