胆碱能过活化状态下“疏肝调神”针法对CUMS抑郁大鼠行为学的影响

目的观察胆碱酯酶抑制剂毒扁豆碱所致的胆碱能过活化状态下,“疏肝调神”针法对慢性不可预知温和应激(CUMS)抑郁模型大鼠前额叶和血清胆碱能相关因子表达和行为学的影响,探讨“疏肝调神”针法治疗抑郁障碍的作用机制。方法采用雄性Sprague Dawley(SD)大鼠60只,随机分为正常组、模型组、电针组、东莨菪碱组(阳性药物组)、毒扁豆碱组(乙酰胆碱酯酶抑制剂组)和电针+毒扁豆碱组,除正常组外进行3 w的造模,成功造模后,予电针或药物干预,持续3 w,观察各组大鼠的体重及糖水偏好实验、强迫游泳实验和新环境抑制进食实验的行为学变化,并应用酶联免疫吸附试验(ELISA)检测前额叶乙酰胆碱酯酶(AChE)、乙酰转移酶(ChAT)、乙酰胆碱(ACh)、去甲肾上腺素(NE)和血清内皮质醇(CORT)的含量变化。结果与正常组比较,模型组大鼠的体重、糖水偏好率显著下降,累计不动时间和延迟进食时间显著延长,AChE、NE含量明显降低,ChAT、ACh、CORT含量明显升高;与模型组比较,电针组和东莨菪碱组大鼠抑郁样行为明显改善,电针组大鼠AChE、NE含量升高,ChAT、ACh、CORT含量明显降低,毒扁豆碱组大鼠抑郁样行为显著加重,AChE、NE含量明显降低,ChAT、ACh、CORT含量明显升高;与毒扁豆碱组比较,电针+毒扁豆碱组大鼠的抑郁样行为明显改善,AChE、NE含量升高,ChAT、ACh、CORT含量明显降低。结论电针可有效改善CUMS抑郁大鼠的抑郁样行为,其作用机制可能是电针参与调控胆碱能代谢,有效解除胆碱能过活化状态,降低机体对应激的易感性而发挥抗抑郁效应的。

Effect of"Shugantiaoshen"acupuncture on behaviors of depressed CUMS rats with cholinergic hyperactivation state

Objective To observe the effect of"Shugantiaoshen"acupuncture on the expression and behavior of cholinergic factors in the frontal lobe and serum of chronic unpredictable mild stress(CUMS)depression model rats with cholinergic hyperactivation state,to explore the mechanism of"Shugantiaoshen"acupuncture in the treatment of depressive disorder.Methods 60 Sprague-Dawley(SD)male rats were divided into the normal group,model group,electroacupuncture group,scopolamine(positive control)group,physostigmine(acetylcholinesterase inhibitor)group and electroacupuncture+physostigmine group.In addition to the normal group,modeling was performed for 3 weeks,after successfully modeling,electroacupuncture and drugs were administrated for 3 weeks except for the normal and model group.The body weight,sucrose intake test,forced swim test and novelty-suppressed feeding test were employed to measure the depressive behaviors.The concentrations of acetylcholinesterase(AChE),acetyltransferase(ChAT),acetylcholine(ACh),norepinephrine(NE)in the prefrontal cortex and cortisol(CORT)in the serum were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with normal group,the body weight and sugar water preference rate of model group were significantly decreased,the cumulative immobility time and delayed feeding time were significantly prolonged,the contents of AChE and NE were significantly decreased,and the contents of ChAT,ACh and CORT were significantly increased.Compared with the model group,the depressed-like behavior of the electroacupuncture group and scopolamine group were significantly improved,the contents of AChE and NE were increased in the electroacupuncture group,and the contents of ChAT,ACh and CORT were significantly decreased.The depressed-like behavior of the physostigmine group was significantly increased,the contents of AChE and NE were significantly decreased,and the contents of ChAT,ACh and CORT were significantly increased in the physostigmine group.Compared with physostigmine group,the depression-like behavior was significantly improved,the contents of AChE and NE were significantly increased,and the contents of ChAT,ACh and CORT were significantly decreased in the electroacupuncture+physostigmine group.Conclusions Electroacupuncture could effectively improve depression-like behavior in CUMS depression model rats,and its underlying mechanism may be that electroacupuncture is involved in regulating cholinergic metabolism,effectively removing cholinergic hyper-activation state,reducing the body′s susceptibility to stress and playing an antidepressant action.