汪进良;刘屏;王东晓;涂海华;陈桂芸;
WANG Jin-liang,LIU Ping,TU Hai-hua,WANG Zhong-xiao,CHEN Gui-yun(Dept of Clinical Pharmacology,General Hospital of PLA,Beijing 100853,China)

• 1:解放军总医院临床药理研究室
• 2:解放军总医院临床药理研究室
• 3:解放军总医院临床药理研究室
• 4:解放军总医院临床药理研究室

摘要(Abstract)：

目的:研究中药复方开心散对慢性应激大鼠行为及海马磷酸化环磷腺苷反应元件结合蛋白(p-CREB)表达的影响。方法:选择Open-filed法评分相近的雄性W istar大鼠,随机分为空白组、模型组、地昔帕明(10mg.kg-1)组、开心散高剂量(8 g.kg-1)组和开心散低剂量(4 g.kg-1)组。采用孤养和慢性不可预见性中等强度应激造成大鼠抑郁模型,观察抑郁大鼠经药物治疗前后的行为学变化及海马p-CREB的免疫组织化学改变。结果:实验第22天,给予应激的各组大鼠体重及糖水摄入量均明显低于空白组,而给予药物治疗的各组大鼠体重及糖水摄入量则明显高于单纯应激组(P<0.01)。开心散4 g.kg-1治疗组大鼠的抑郁行为较模型组有显著改善,水平运动和垂直运动得分均明显提高(P<0.01),其海马CA1,CA3和DG区p-CREB的表达也均明显高于模型组(P<0.05和P<0.01)。结论:开心散可提高慢性抑郁大鼠海马CA1,CA3和DG区p-CREB的表达,改善大鼠的抑郁样行为。
Objective: To study the effects of Kaixinsan on behavior and expression of p-CREB in hippocampus of the chronic stress rats.Method: The male Wistar rats which gained the similar scores by Open-field test were selected,then the depression model rat was produced by separation and chronic unpredictable mild stress.Open-field test was performed to detect the behavior of rats and immunohistochemistry was used to observe the changes of p-CREB expression in hippocampus.Result: On the 22nd day,the body weight and sacchar-intake of the depression model rats were all lower than those of the normal rats and the body weight and sacchar-intake of the rats treated by drugs were higher compared with model rats(P<0.01).The depressive behavior in Kaixinsan 4 g·kg-1 group was significantly improved compared with the model group,the crossing scores and rearing scores were all increased(P<0.01)and the expression of p-CREB in CA1,CA3 and DG in hippocampus was higher than that in the model group(P<0.05 and P<0.01).Conclusion: Kaixinsan might improve depressive behavior by increasing expression of p-CREB in CA1,CA3 and DG in hippocampus of the chronic stress rats.

关键词(KeyWords)： 抑郁症;开心散;海马;p-CREB
depression;Kaixinsan;hippocampus;p-CREB

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(90209036)

作者(Authors): 汪进良;刘屏;王东晓;涂海华;陈桂芸;
WANG Jin-liang,LIU Ping,TU Hai-hua,WANG Zhong-xiao,CHEN Gui-yun(Dept of Clinical Pharmacology,General Hospital of PLA,Beijing 100853,China)

参考文献(References)：

• [1]汪进良,刘屏,陈孟莉,等.开心散对强迫游泳小鼠中枢神经递质及血浆皮质醇的影响[J].北京中医药大学学报,2005,28(2):36.
• [2]Katz R J,Roth K A,Carroll B J.Acute and chronic stress effectson Open-field activity in the rat:implications for a model of de-pression[J].Neurosci Biobehav Rev,1981,5:247.
• [3]Goda S,Takano K,Yamagata Y,et al.Effect of extra N-terminalresidues on the stability and folding of human lysozyme expressedin pichia pastoris[J].Protein Eng,2000,13(4)L:299.
• [4]Willner P.Validity,reliability and utility of the chronic mildstress model of depression:a 10-year review and evaluation[J].Psychopharmacology(Berl),1997,134:319.
• [5]Finkbeiner S.Calcium regulation of the brain-derived neurotrophinfactor gene[J].Cell Mol Life Sci,2000,57(3):394.
• [6]Nakagawa S,Kim J E,Lee R,et al.Regulation of neurogenesisin adult mouse hippocampus by cAMP and the cAMP response ele-ment-binding protein[J].J Neurosci,2002,22(9):3673.