针刺对抑郁症大鼠海马SNARE蛋白介导突触前谷氨酸释放的影响

摘要

目的：探讨针刺对抑郁症的治疗作用及其可能的治疗靶点。方法采用长期不可预见的温和性刺激建立大鼠抑郁症模型。成功造模后，给予利鲁唑和针刺治疗，观察各组大鼠行为学的变化，测定海马组织谷氨酸的含量变化；应用Western印迹和荧光定量PCR检测突触小体相关蛋白（SNAP）-25、突触小泡膜相关蛋白（VAMP）1、VAMP2、VAMP7和syntaxin1蛋白及相应mRNA表达。结果与空白组相比，应激后大鼠的活动能力、体重和蔗糖消耗量明显下降（P＜0.05）；海马组织谷氨酸含量显著升高（P＜0.01）；而经利鲁唑和针刺治疗后，活动能力、体重和蔗糖消耗量升高；海马组织谷氨酸含量下降。 Western印迹和RT-PCR结果显示：模型组大鼠的SNAP-25、VAMP1、VAMP2、VAMP7和syntaxin1表达量显著高于空白组（P＜0.05）；与模型组相比，利鲁唑和针刺组均能降低SNAP-25、VAMP1、VAMP2、VAMP7和syntaxin1表达水平，且利鲁唑组与针刺组对各检测指标的影响均无显著性差异（P＞0.05）。结论针刺对谷氨酸释放有明显的调节作用，可溶性NSF附着蛋白受体（SNARE）介导的突触前谷氨酸释放在抑郁症的发病以及针刺抗抑郁过程中有重要作用，可能是针刺抗抑郁的靶点之一。%Objective To investigate the therapeutic effect of acupuncture on depression and its related possible therapeutic target . Methods Depressive disorder model was induced by exposure to chronic unpredictable stress using Sprague Dawley rats .Acupuncture stim-ulation and riluzole were used to treat the depressed rats .Behavior changes , hippocampucal glutamate content and glutamate-glutamine cycle related genes SNARE , were analyzed before and after therapy .Results Compared with the blank group , the rats showed horizontal or verti-cal movements, weight and sucrose consumption significantly decreased (P <0.05), and the glutamate content in hippocampus was in-creased (P<0.05).After riluzole and acupuncture treatment , horizontal or vertical movements , weight and sucrose consumption were signif-icantly increased (P<0.05), and the glutamate content in hippocampus was decreased .Western blot and RT-PCR showed that the expres-sion of SNAP-25, VMAP7, VMAP1, VMAP2 and syntaxin1 in the model group were significantly higher than those of the blank group (P<0.05).Compared with the model group, riluzole and acupuncture could reduce the expression levels of SNAP-25, VMAP1, VMAP7, VMAP2 and syntaxin1,and there were no significant differences between the acupuncture and riluzole group (P>0.05).Conclusions Acu-puncture has a significant regulatory effect on glutamate release , SNARE protein mediated presynaptic release of glutamate plays an important role in depression , and it may be one of the targets of antidepression .