针刺对强迫游泳应激大鼠海马c-jun氨基末端激酶信号通路的影响  

Effect of Acupuncture Intervention on c-jun N-terminal Kinase Signaling in the Hippocampus in Rats with Forced Swimming Stress

作　　者：郭郁[1] 许珂[2] 包伍叶[3] 王瑜[1] 张旭辉[1] 许明敏[1] 于淼[1] 张春涛[1] 赵冰骢 邬继红[1] 图娅[1] 

机构地区：[1]北京中医药大学针灸推拿学院,北京100029 [2]北京大学第六医院,北京100191 [3]内蒙古民族大学附属医院,通辽028007

出　　处：《针刺研究》2016年第1期18-23,共6页Acupuncture Research

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

摘　　要：目的:观察针刺对强迫游泳应激大鼠海马c-jun氨基末端激酶(JNK)信号转导通路影响,探讨针刺抗抑郁的作用机制。方法:SD大鼠随机分为空白组、空白+JNK通路阻断剂(SP 600125,以下简称SP)组、模型组、模型+SP组、针刺组、针刺+SP组、氟西汀组、氟西汀+SP组,每组6只。采用强迫游泳应激结合孤养法造模。针刺干预选取"百会""印堂"穴,每次20min,每天1次,共治疗2d;阳性对照药物给予氟西汀1.8mg/kg灌胃,每天1次,共治疗2d。通过游泳不动时间对大鼠进行行为学评价;采用Western blot法检测海马中JNK上游激酶MKK 4和MKK 7、JNK、磷酸化JNK(p-JNK)蛋白表达。结果:与空白组比较,空白+SP组游泳不动时间差异无统计学意义(P>0.05),模型组游泳不动时间显著增加(P<0.01);与模型组比较,模型+SP组、针刺组、针刺+SP组、氟西汀组、氟西汀+SP组游泳不动时间明显缩短(P<0.05,P<0.01)。不同组别之间JNK蛋白表达水平差异无统计学意义(均P>0.05)。与空白组比较,模型组海马中MKK 4、MKK 7、p-JNK蛋白表达显著升高(均P<0.01);与模型组比较,氟西汀+SP组MKK 4、MKK 7蛋白表达显著降低(均P<0.05),其余组有降低趋势,但差异无统计学意义(均P>0.05),模型+SP组、针刺组、针刺+SP组、氟西汀组、氟西汀+SP组p-JNK蛋白表达显著降低(P<0.05,P<0.01)。结论:针刺治疗能降低急性应激模型大鼠海马JNK的磷酸化水平及蛋白表达,有效抑制JNK信号转导通路活性,进而改善强迫游泳应激抑郁模型大鼠的行为学症状,这可能是针刺发挥抗抑郁效应的分子机制之一。Objective To observe the effect of acupuncture on c-jun N-terminal Kinase（JNK）signaling in the hippocampus in rats with forced-swimming stress,so as to reveal its underlying mechanism in relieving depression-like motor response.Methods Forty-eight Sprague-Dawley rats were randomly divided into 8groups as control,control＋JNK inhibitor（SP600125）,model,model＋SP 600125,acupuncture,acupuncture＋SP 600125,Fluoxetine（an anti-depressant）,and Fluoxetine＋SP 600125（n=6in each group）.The depression-like behavior（immobility）model was established by forcing the rat to swim in aglass-cylinder and solitary raise.Acupuncture stimulation was applied to＂Baihui＂（GV 20）and ＂Yintang＂（GV 29）for 20 min before forced swimming and once again 24 hlater.The rats of the Fluoxetine and Fluoxetine＋SP 600125 groups were treated by intragastric administration of fluoxetine 10mL（1.8mg）/kg before forced swimming and once again 24 hthereafter.The rats of the model＋ SP 600125 and acupuncture＋SP 600125 groups were treated by intraperitoneal injection of SP 600125（10mg/kg）90min before forced swimming and 30 min before acupuncture intervention,respectively.The immobility duration of rats in the water glass-cylinder was used to assess their depression-like behavior response.The expression levels of protein kinase kinase 4（MKK 4）,MKK 7,JNK,and phosphorylated JNK（p-JNK）in the hippocampus were detected by Western blot.Results Compared to the control group,the duration of immobility,and the expression levels of hippocampal MKK 4,MKK 7,and p-JNK proteins were significantly increased in the model group（P〈0.01）.While in comparison with the model group,the duration of immobility in the model＋SP 600125,acupuncture,acupuncture＋SP 600125,Fluoxetine and Fluoxetine＋SP 600125 groups,the expression levels of hippocampal MKK 4and MKK 7proteins in the Fluoxetine＋SP 600125 group,and those of p-JNK protein in the acupuncture,acupuncture＋SP 600125,model＋SP 600125,Fluoxetine and Fluoxetine＋

关 键 词：针刺 海马 强迫游泳应激 抑郁样行为反应 C-JUN氨基末端激酶 

分 类 号：R245.311[医药卫生—针灸推拿学]