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

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.

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

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-HT_{1A/ 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-HT_1A mRNA level declined while 5-HT_2A 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-HT_1Areceptor mRNA in hippocampus and 5-HT_2A receptor mRNA in cerebral cortex, meanwhile reducing 5-HT_2A receptor mRNA in hippocampus and 5-HT_1A receptor mRNA in cerebral cortex.