手针干预对慢性温和不可预知应激模型大鼠前额叶皮层细胞外调节蛋白激酶1/2和脑源性神经营养因子表达的影响  

Effect of Acupuncture Intervention on Depression Behavior and Expression of ERK 1/2 and BDNF in Prefrontal Cortex in Chronic Unpredictable Mild Stress Induced Depression Rats

作　　者：李想 许明敏 姜会梨 卢峻[1,2] 张旭辉[1] 赵冰骢 杨昕婧[1,2] 孙阳 高兴周 梁星辰 俞秋云 冯世醒 李宇飞 于淼[1] 图娅[1,2] LI Xiang;XU Ming min;JIANG Hui-li;LU Jun;ZHANG Xu-hui;ZHAO Bing-cong;YANG Xin-jing;SUN Yang;GAO Xing-zhou;LIANG Xing-chen;YU Qiu-yun;FENG Shi-xing;LI Yu-fei;YU Miao;TU Ya(School of Acupuncture-moxibustion and Tuina,Beijing University of Chinese Medicine,Beijing 100029,China;Re-search Center of Mental and Neurological Disorders,School of Acupuncture-moxibustion and Tuina,Beijing University of Chinese Medicine,Beijing 100029;Chengdu University of Chinese Medicine,Chengdu 610075)

机构地区：[1]北京中医药大学针灸推拿学院,北京100029 [2]北京中医药大学针灸推拿学院神经精神疾患研究中心,北京100029 [3]成都中医药大学,成都610075

出　　处：《针刺研究》2018年第11期705-710,共6页Acupuncture Research

基　　金：国家自然科学基金项目(No.81173334;81373729;81574070)

摘　　要：目的:观察在阻断剂PD 98059特异性阻断下,针刺对慢性温和不可预知应激(CUMS)大鼠前额叶细胞外调节蛋白激酶(ERK)1/2、磷酸化ERK 1/2(p-ERK 1/2)和脑源性神经营养因子(BDNF)蛋白表达水平的影响,探讨针刺抗抑郁的机制。方法:SD大鼠随机分为空白组、模型组、针刺组、氟西汀组、模型+DMSO组、模型+ERK通路阻断剂(简称阻断剂)组、针刺+阻断剂组、氟西汀+阻断剂组,每组8只。采用慢性温和不可预知应激方法造模21d。针刺干预选取"百会""印堂",于每日造模前30 min进行,每次10min,共21d。氟西汀组与氟西汀+阻断剂组于造模前30min给予氟西汀灌胃。模型+DMSO组于造模前1h给予DMSO侧脑室注射,模型+阻断剂组、针刺+阻断剂组、氟西汀+阻断剂组于造模前1h予侧脑室注射阻断剂。通过糖水消耗实验对大鼠进行行为学评价,蛋白免疫印迹法检测大鼠前额叶ERK 1/2、p-ERK1/2和BDNF的蛋白表达水平。结果:与空白组比较,模型组大鼠糖水消耗量及前额叶p-ERK 1/2、BDNF蛋白表达水平均明显下降(P<0.01)。与模型组比较,针刺组、氟西汀组糖水消耗量、p-ERK 1/2蛋白表达水平均明显上调(P<0.01),BDNF蛋白表达水平上调(P<0.05,P<0.01),模型+阻断剂组糖水消耗量减少(P<0.05)。与针刺组比较,针刺+阻断剂组糖水消耗量、p-ERK 1/2蛋白表达水平均明显下调(P<0.01)。各组大鼠ERK 1/2蛋白表达水平差异均无统计学意义(P>0.05)。结论:针刺可能是通过上调前额叶ERK1/2的磷酸化水平,增加BDNF蛋白表达,改善CUMS模型大鼠抑郁样行为,从而发挥抗抑郁效应。Objective To investigate the effect of acupuncture intervention on the depression behavior and expression of extracellular signal-regulated protein kinases（ERK 1/2）,p-ERK 1/2 and brain-derived neurotrophic factor（BDNF）in the prefrontal cortex of chronic unpredictable mild stress（CUMS）induced depression rats,so as to explore its antidepressant mechanism.Methods Sixty-four male SD rats were randomly divided into control,model,acupuncture,Fluoxetine,model＋ Dimethyl sulfoxide（DMSO）,model＋ PD 98059（an ERK pathway inhibitor）,acupuncture＋ PD 98059 and Fluoxetine＋ PD 98059 groups（n=8 rats in each）.The CUMS depression model was established by using chronic mild and unpredictable stress methods for 21 days.Manual acupuncture stimulation was applied to＂Baihui＂（GV 20）and＂Yintang＂（GV 29）for 10 min before modeling,once daily for 21 days.Fluoxetine hydrochloride suspension（1.8 mg·kg^（-1）·d^（-1））was given to rats of the Fluoxetine group and Fluoxetine＋ PD 98059 group by gavage 30 min before CUMS.PD 98059（dissolved in DMSO,10 μL）was administered to rats of model＋ PD 98059 group,acupuncture＋ PD 98059 and Fluoxetine＋ PD 98059 group,and DMSO（10μL）to rats of model＋DMSO group by intracerebroventricular injection 1 hbefore CUMS.Sucrose consumption test was carried out to evaluate the depressive behavior.Western blot was performed to detect the expression of ERK 1/2,p-ERK 1/2 and BDNF of prefrontal cortex.Results Compared with the control group,the sucrose consumption and the expression levels of p-ERK 1/2 and BDNF protein in the prefrontal cortex were significantly reduced in the model and model＋DMSO group（P〈0.01）.After the intervention,modeling induced decrease of the sucrose consumption,and p-ERK 1/2 and BDNF expression was significantly up-regulated in both acupuncture and Fluoxetine groups（P〈0.01,P〈0.05）,but not in the model＋PD 98059,Fluoxetine＋PD 98059 and acupuncture＋PD 98059 groups（P〈0.05）.No significant differences were

关 键 词：针刺 抑郁症 慢性温和不可预知应激 细胞外调节蛋白激酶 脑源性神经营养因子 阻断剂PD 98059 

分 类 号：R246.6[医药卫生—针灸推拿学]