开心解郁汤对抑郁症模型大鼠脑皮质5-HT水平和海马与大脑皮层5-HTA亚型受体mRNA表达的影响  

Effects of Kaixin Jieyu Decoction on Changes of 5-HT Contents and Gene-expression of 5-HT Receptor Subtypes in Brain of Rats with Depression

作　　者：方素萍[1] 王彦云[2] 崔翰明[2] 黄世敬[2] 

机构地区：[1]中国中医科学院广安门医院分子生物室,北京100053 [2]中国中医科学院广安门医院中药研发中心,北京100053

出　　处：《中国实验方剂学杂志》2012年第18期148-153,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(30672696);北京市自然科学基金项目(7093129)

摘　　要：目的:观察具有培元开郁作用的"开心解郁汤"对大鼠脑皮质中5-羟色胺(5-HT)水平和海马及大脑皮层5-HT1A受体和5-HT2A受体mRNA表达以及行为学能力的影响。方法:SD大鼠随机分为正常对照组、抑郁症组、抑郁症+中药组、抑郁症+西药组,采用慢性不可预见性温和应激方法(CUMS)造成抑郁症大鼠模型。造模同时开始给药,中药组给予开心解郁汤(按生药量计,22 g.kg-1,西药组给予盐酸氟西汀2.4 mg.kg-1,其余各组给同体积生理盐水,每日1次,连续ig给药22 d。分别于实验前、抑郁1,8,15,22 d记录大鼠体重;并观察大鼠行为学变化。于22 d后分取脑皮质,应用高效液相色谱技术分析脑皮质中5-HT水平变化;于22 d后分取脑皮质和海马区,采用实时荧光定量PCR技术,测定大鼠海马及脑皮质中5-HT1A和5-HT2A受体mRNA水平改变。结果:与正常对照组相比,抑郁造模各组体重增长明显减慢,体重增加数和糖水消耗量均下降,旷场实验测定水平活动和垂直活动次数均下降(P<0.01,P<0.05),给与中药干预后,大鼠体重增长有所增快,与抑郁模型组比较有显著差异。糖水消耗量、水平活动和垂直活动次数均较模型组明显增加(P<0.01,P<0.05);同时抑郁造模后5-HT总体水平呈现下降,给予中药和西药治疗后5-HT水平有显著升高(P<0.05)。模型组大鼠海马组织中5-HT1AR mRNA水平下降,而5-HT2AR mRNA水平升高,中药及西药治疗后均可不同程度地降低;而在脑皮质中5-HT1AR和5-HT2AR mRNA水平的改变则呈现相反的变化。结论:CUMS可引起大鼠行为学改变并致体重减轻和行为学改变,造成大鼠抑郁模型。开心解郁汤可以降低海马中5-HT1A受体mRNA和脑皮质中5-HT2A受体mRNA水平,同时升高海马中5-HT2A受体mRNA和脑皮质中5-HT1A受体mRNA水平,而部分实现其对抑郁症的治疗作用。Objective：To investigate the effects of Kaixin Jieyu decoction（KJD） on changes of 5-HT contents and the gene-expression of 5-HT receptor subtypes in the brain of rats with depression.Method：SD rats were randomly divided into 4 groups：control,depression model（CUMS）,CUMS＋KJD,CUMS＋fluoxetine.The depression model of rat was established by chronic unpredictable mild stress（CUMS）.The treatments were given contemporarily,KJD group was given crud drug 22 g · kg-1,as fluoxetine was given 2.4 mg · kg-1,and the other groups were given same volume normal saline for once a day for 22 days.Regularly changes on body weight were evaluated and the behaviors changes were recorded after 1,8,15,22 days;22 d later,the cerebral cortex and hippocampus were acquired respectively,the content of monoamines neurotransmitter 5-HT in cerebral cortex was determined by HPLC-ECD and the 5-HT1A/ 2A receptor mRNA were determined by real-time PCR.Result：Compared with control group,the growth of body weight was significantly decreased in those CUMS-induced groups,the consumption of hedonia and number of the horizontal and vertical activity were decreased also（P〈0.01,P〈0.05）,while increased gradually（P〈0.05） in the KLD group.The total 5-HT levels in cerebral cortex were declined in CUMS-induced groups,while those in KJD and fluoxetine groups were increased remarkable（P〈0.05）.In cerebral cortex of the control group,5-HT1A mRNA level declined while 5-HT2A mRNA level increased,both KJD and fluoxetine showed different decreasing effects.As those in hippocampus,changes were reversed.Conclusion：The depression model of rat can be established by CUMS.These CUMS-induced depression state can be ameliorated by KJD,and possible mechanism consists of improving the level of 5-HT in cerebral cortex and increasing 5-HT1Areceptor mRNA in hippocampus and 5-HT2A receptor mRNA in cerebral cortex,meanwhile reducing 5-HT2A receptor mRNA in hippocampus and 5-HT1A receptor mRNA in cerebral cortex.

关 键 词：开心解郁汤 抑郁症 5-HT1A和5-HT2A受体 海马 脑皮质 

分 类 号：R285.5[医药卫生—中药学]