针刺对BPD心境稳定作用的海马兴奋/抑制中枢机制研究

Bipolar disorder (BPD) is a common psychiatric disease characterized with high prevalence, high recurrence rate, high morbidity, and high mortality. BPD has been a clinical challenge because of its easy transition from depression phase to manic phase during the course, and the treatment limitation of mood stabilizing drugs. Acupuncture has been used in the treatment of BPD for its good two-phase adjustment function. Our preliminary study has also indicated that acupuncture has some mood stabilizing effect (i.e., both anti-depression effect and anti-manic effect). The current study will focus on Glu/GABA activation/inhibition regulation system. We will investigate the molecular mechanisms of the pathological alteration of this regulation system by examining the synthesis of GABA, the re-uptake of GABA and Glu, and the expression of glutamateNMDA receptor and GABAA receptor proteins and mRNAs. We aim to elucidate the mechanisms on how acupuncture stabilizes the mood and to identify the molecular targets so to provide a scientific and application basis for the acupuncture treatment of BPD.

双相情感障碍（BPD）是精神科常见疾病，具有高患病率,高复发率,高致残率，高死亡率的特点。病程中抑郁相和躁狂相之间极易转化的特殊性及西药心境稳定剂治疗的局限性使其成为临床难题。针刺疗法因其具有良性双向调节作用被用于BPD的治疗，前期研究证实其确有一定的心境稳定作用（即兼有抗抑郁作用和抗躁狂作用）。本研究拟以Glu/GABA兴奋/抑制平衡调节系统为切入点，从GABA的合成、GABA和Glu的再摄取、谷氨酸NMDA受体和GABAA受体的蛋白表达和mRNA表达水平等多个环节多个层面系统研究Glu/GABA兴奋/抑制平衡调节系统病理改变的分子机制，探讨针刺心境稳定作用机制及分子靶点，为针刺治疗BPD提供科学依据和应用基础。

双相情感障碍（BPD）是精神科常见疾病，具有高患病率,高复发率,高致残率，高死亡率的特点。病程中抑郁相和躁狂相之间极易转化的特殊性及西药心境稳定剂治疗的局限性使其成为临床难题。针刺疗法因其具有良性双向调节作用被用于BPD的治疗，前期研究证实其确有一定的心境稳定作用（即兼有抗抑郁作用和抗躁狂作用）。本项目以Glu/GABA平衡调节系统为切入点，以海马谷氨酸脱羧酶(GAD65、GAD67)、谷氨酸转运体（EAAT3）、GABA转运体1（GAT1）、NMDA受体亚单位NR1, NR2A, NR2B、GABAA受体的mRNA和蛋白表达水平为主要观察指标，从GABA的合成、GABA和Glu的再摄取、谷氨酸NMDA受体和GABAA受体的蛋白表达水平等多个环节多个层面系统研究Glu/GABA兴奋/抑制平衡调节系统在躁狂/抑郁状态下病理改变的分子机制，探讨针刺心境稳定作用（即兼有抗抑郁作用和抗躁狂作用）机制及分子靶点。本研究显示针刺百会、内关、三阴交穴抗抑郁作用和抗躁狂作用（即心境稳定作用）的神经生物学机制之一是调整海马脑区GLU和GABA的含量失衡。其抗抑郁作用与增加海马GAD65、EAAT3表达、减少GAT1、NR1和NR2A的表达有关，而其抗躁狂作用与增加海马GAD65表达、减少GAT1和NR2B表达有关，初步揭示了针刺心境稳定作用（即兼有抗抑郁作用和抗躁狂作用）机制及分子靶点。