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开心解郁汤对大鼠抑郁模型行为、单胺类神经递质水平及脑内5-羟色胺受体亚型表达的影响。

Effects of Kaixin Jieyu Decoction () on behavior, monoamine neurotransmitter levels, and serotonin receptor subtype expression in the brain of a rat depression model.

作者信息

Huang Shi-jing, Zhang Xian-hui, Wang Yan-yun, Pan Ju-hua, Cui Han-ming, Fang Su-ping, Wu Wei, Zheng Jun, Li Duo-jiao, Bai Ge

机构信息

Traditional Chinese Medicine Research and Development Center, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.

出版信息

Chin J Integr Med. 2014 Apr;20(4):280-5. doi: 10.1007/s11655-014-1343-0. Epub 2014 Feb 24.

DOI:10.1007/s11655-014-1343-0
PMID:24567255
Abstract

OBJECTIVE

To determine the mechanisms underlying the anti-depressant effects of Kaixin Jieyu Decoction (, KJD) by investigating the effects of KJD on behavior, monoamine neurotransmitter levels, and serotonin (5-HT) receptor subtype expression in the brain in a rat model of depression.

METHODS

The rat depression model was established using chronic unpredictable mild stress (CUMS). Forty-eight Sprague Dawley rats were randomly divided into control, depression model (CUMS), CUMS+KJD (7.7 g/kg(-1)·d(-1) of crude drug), and CUMS+fluoxetine (2.4 mg/kg(-1)·d(-1)) groups (n=12 in each group), and the treatments lasted for 21 days. We regularly evaluated body weight, sucrose consumption, and horizontal and vertical activity scores in open-field tests. The content of the monoamine neurotransmitters 5-HT, norepinephrine (NE), and dopamine (DA) and the DA metabolite homovanillic acid in the cerebral cortex, and 5-HT1A and 5-HT2A receptor mRNA in the cerebral cortex and the hippocampus, were determined respectively by high-performance liquid chromatography-coularray electrochemical detector and real-time polymerase chain reaction.

RESULTS

Compared with the control group, CUMS rats showed a variety of depression-like behavioral changes, including a significant reduction in body weight, sucrose consumption, and horizontal and vertical activity scores in open-field tests (P<0.05 or P<0.01), and a significant decrease in 5-HT and NE levels and 5-HT2A receptor mRNA expression. In contrast, they showed a significant increase in 5-HT1A receptor mRNA expression in the cerebral cortex. In the hippocampus, 5-HT1A receptor mRNA expression was lower whereas 5-HT2A receptor mRNA expression was higher than in the control group (P<0.05 or P<0.01). Treatment with KJD or fluoxetine partially attenuated these changes (P<0.05 or P<0.01).

CONCLUSION

KJD could normalize the levels of 5-HT and NE and adjust the balance of 5-HT1A and 5-HT2A receptor expression in rat cerebrum, and this may be one of mechanisms of antidepressant effects of KJD.

摘要

目的

通过研究开心解郁汤(KJD)对抑郁大鼠模型行为、单胺类神经递质水平及脑内5-羟色胺(5-HT)受体亚型表达的影响,确定开心解郁汤抗抑郁作用的潜在机制。

方法

采用慢性不可预测温和应激(CUMS)建立大鼠抑郁模型。将48只Sprague Dawley大鼠随机分为对照组、抑郁模型组(CUMS)、CUMS+KJD组(生药7.7 g/kg-1·d-1)和CUMS+氟西汀组(2.4 mg/kg-1·d-1)(每组n = 12),治疗持续21天。我们定期评估体重、蔗糖消耗量以及旷场试验中的水平和垂直活动得分。分别采用高效液相色谱-柱阵列电化学检测器和实时聚合酶链反应测定大脑皮质中单胺类神经递质5-HT、去甲肾上腺素(NE)、多巴胺(DA)以及DA代谢产物高香草酸的含量,以及大脑皮质和海马中5-HT1A和5-HT2A受体mRNA的表达。

结果

与对照组相比,CUMS大鼠表现出多种抑郁样行为变化,包括体重显著降低、蔗糖消耗量减少、旷场试验中的水平和垂直活动得分降低(P<0.05或P<0.01),5-HT和NE水平以及5-HT2A受体mRNA表达显著下降。相反,它们大脑皮质中5-HT1A受体mRNA表达显著增加。在海马中,5-HT1A受体mRNA表达低于对照组,而5-HT2A受体mRNA表达高于对照组(P<0.05或P<0.01)。KJD或氟西汀治疗部分减轻了这些变化(P<0.05或P<0.01)。

结论

开心解郁汤可使大鼠大脑中5-HT和NE水平正常化,并调节5-HT1A和5-HT2A受体表达的平衡,这可能是开心解郁汤抗抑郁作用的机制之一。

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