开心散对小鼠抑郁样行为及海马中脑源性神经营养因子的影响  

Effect of Kaixin-San on depression behavior and hippocampal brain-derived neurotrophic factor in mice

作　　者：刘明月[1,2] 董宪喆[2] 张岗强[2] 辛海量[3] 刘屏[2] 胡园[2] 

机构地区：[1]河北北方学院药学系,张家口075000 [2]解放军总医院临床药理研究室,北京100853 [3]第二军医大学中医系,上海200433

出　　处：《第二军医大学学报》2012年第12期1319-1323,共5页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(81173579)~~

摘　　要：目的观察开心散对悬尾模型小鼠行为学、脑内单胺类递质及海马中脑源性神经营养因子(BDNF)水平的影响,探究开心散的抗抑郁效果与海马中BDNF含量的相关性。方法采用小鼠悬尾实验,观察不同剂量开心散对小鼠不动时间的影响;HPLC法测定脑内去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)的含量;蛋白质印迹法检测小鼠海马中cAMP反应元件结合蛋白(CREB)、p-CREB、BDNF的表达;RT-PCR检测海马中BDNF mRNA的表达,Pearson相关性检验确定开心散的抗抑郁作用与海马中BDNF蛋白和mRNA水平的相关性。结果开心散可缩短悬尾小鼠不动时间(P<0.05),可增加小鼠脑内单胺类递质(DA、5-HT)和海马中CREB、p-CREB、BDNF的含量(P<0.05),其抗抑郁作用与海马中BDNF水平呈良好相关性(蛋白质:r=-0.694,P<0.01;mRNA:r=-0.547,P<0.01)。结论开心散对小鼠的抗抑郁作用与海马BDNF水平呈正相关性,提示开心散可能通过增加海马中BDNF表达发挥抗抑郁作用。Objective To investigate the effect of Kaixin-San （KXS） on behavior, brain monoamine transmitters, and hippocampal brain-derived neurotrophic factor （BDNF） in mice receiving tail suspension test （TST）, so as to explore the correlation of the antidepressant effect of KXS and hippocampal BDNF level. Methods The effect of KXS on the immobility time of mice in the TST was observed. The levels of norepinephrine （NE）, dopamine （DA） and 5 hydroxytryptamine （5-HT） in the brain were determined by high-performance liquid chromatography （HPLC）. Western blotting analysis was used to examine the expressions of cAMP-response element-binding protein （CREB）, p CREB, and BDNF in the hippocampus. BDNF mRNA expression was also examined by RT-PCR. Pearson＇s correlation analysis was used to evaluate relationship between anti-depression effect of Kaixin-San and hippocampal BDNF level. Results KXS reduced the immobility time of mice in the TST （P〈0.05）; it also increased the brain levels of monoamine transmitters （DA and 5-HT） and hippocampal levels of CREB, p-CREB and BDNF compared with the control mice （P〈0. 05）. Moreover, the anti-depression effect of KXS was correlated with BDNF level （protein：r=--0. 694, P〈0.01） mRNA .. r=- 0. 547, P〈0.01） in the hippocampus. Conclusion The anti- depression effect of KXS is positively correlated with the hippocampal BDNF level, indicating KXS may exert anti-depression effect via increasing hippocampal BDNF.

关 键 词：开心散 抗抑郁药 海马 CAMP反应元件结合蛋白质 脑源性神经营养因子 

分 类 号：R971.43[医药卫生—药品]