电针对抑郁症大鼠海马CREB-BDNF受体后信号转导通路的作用

Effect of electroacupuncture on CREB-BDNF postreceptor signal transduction pathway in hippocampus of depression rats

目的探讨电针对抑郁症大鼠的治疗作用及海马cAMP反应元件结合蛋白(CREB)、脑源性神经营养因子(BDNF)的影响。方法SD成年大鼠32只随机分为空白组、模型组、针刺组(合谷+太冲)和药物组(盐酸氟西汀),每组8只。空白组进行正常饲养,不给予其他处理;模型组大鼠采用长期不可预见性温和刺激造成抑郁症模型;电针组大鼠造模后电针合谷穴和太冲穴,每日1次,每次15min,左右两侧穴位交替进行,持续21d。药物组大鼠造模后进行氟西汀灌胃,每日1次,持续3w。应激后第7、14、22天观察大鼠Openfield行为学的变化,应激后22d取材观察海马神经元形态结构、BDNF和CREB的表达。结果(1)应激后第7、14、22天模型组大鼠水平运动及垂直运动较应激前有不同程度的减弱,针刺组于应激后第14天可有效地改善抑郁型大鼠模型的行为学表现,其效果优于药物组(P<0.05)。(2)模型组海马齿状回神经元排列散乱,可见明显肿胀、固缩、变性、脱落等病理改变;针刺组和药物组大鼠海马神经元的病变程度较模型组有不同程度的减轻。(3)模型组大鼠BDNF阳性细胞数量较空白组明显减少(P<0.05),针刺组和药物组海马BDNF和CREB的表达较模型组上调(P<0.05)。结论针刺能改善抑郁症大鼠的行为学及海马神经元的病理变化,CREB-BDNF受体后信号转导通路是针刺抗抑郁的重要途径和作用靶点之一。

Objective To explore the therapeutic effect of electroacupuneture on depresssion rats and cyclic adenosine monophos- phate （cAMP） response element binding protein （CREB） and brain-derived neurotrophie factor （BDNF）. Methods Thirty-two adult Sprague-Dawley rats were divided randomly into control, model, electroacupuncture （EA） and medicine groups, 8 rats in each group. Rats in control group did not receive any other stimulation, and rats in model group were made depression by the chronic mild stress. In EA group, rats were given EA stimulation for 15 minutes, once per day for 3 w, following stress stimulation. Rats in medicine group were treated with fluoxetine hydrochloride for 3 w. Changes of open-field behavior of the rats were observed in the 7th, 14th and 22th d following stress. Morphological changes of hippocampus neurons and the expression of CREB and BDNF were measured in the 22th d. Results （ 1 ） The open field behavior of the depression rats decreased significantly following stress, and EA treatment effectively improved it, which was better than that of the antidepressant（ P 〈0.05 ）. （2） In the depression rats, neurons in the hippocampus were dispersedly distributed in the dentate gyrus （ DG ）, which showed edema, atrophy and denaturation., Both EA and antidepressant treatment improved the neuronal damage in the DG. （3） The number of BDNF positive neurons in model group were remarkably decreased compared with that of control group. In EA group and medicine group, both expressions of CREB and BDNF in the hippocampus were up-regulated obviously（ P 〈 0. 05 ）. Conclusions Acupuncture could improve significantly the changes of the behavior, pathological changes of neurons in the hippocampus, and CREB-BDNF postreceptor signal transduction pathway may be an important approach and target of acupuncture in treating depression.