龙牡桂枝汤及其拆方对注意缺陷多动障碍模型大鼠下丘脑-垂体-肾上腺轴的影响

唐彦; 程艳; 景晓玉; 徐寅

doi:10.13422/j.cnki.syfjx.20200603

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龙牡桂枝汤及其拆方对注意缺陷多动障碍模型大鼠下丘脑-垂体-肾上腺轴的影响

药理 | 更新时间：2021-02-09

- 龙牡桂枝汤及其拆方对注意缺陷多动障碍模型大鼠下丘脑-垂体-肾上腺轴的影响
- Effect of Longmu Guizhi Decoction and Its Disassembled Prescription on Hypothalamic-Pituitary-Adrenal Axis in Rats with Attention Deficit Hyperactivity Disorder
- 中国实验方剂学杂志 2020年26卷第9期页码：23-28
- 作者机构：
  
  云南中医药大学　临床医学院，昆明　 650500
- 作者简介：
  
  *唐彦，博士，教授，从事小儿神经精神疾病的中医证治研究，E-mail：ytyj0812@126.com
- 基金信息：
  
  国家自然科学基金项目(81760880);云南省科技计划项目(2017FF116-025)
- DOI：10.13422/j.cnki.syfjx.20200603
  中图分类号： R2-0; R22; R285.5; R289
- 纸质出版日期：2020-05-05，
  
  网络出版日期：2019-12-06，
  
  收稿日期：2019-08-05，
- 稿件说明：
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唐彦, 程艳, 景晓玉, 等. 龙牡桂枝汤及其拆方对注意缺陷多动障碍模型大鼠下丘脑-垂体-肾上腺轴的影响[J]. 中国实验方剂学杂志, 2020,26(9):23-28.

Yan TANG, Yan CHENG, Xiao-yu JING, et al. Effect of Longmu Guizhi Decoction and Its Disassembled Prescription on Hypothalamic-Pituitary-Adrenal Axis in Rats with Attention Deficit Hyperactivity Disorder[J]. Chinese Journal of Experimental Traditional Medical Formulae, 2020,26(9):23-28.
唐彦, 程艳, 景晓玉, 等. 龙牡桂枝汤及其拆方对注意缺陷多动障碍模型大鼠下丘脑-垂体-肾上腺轴的影响[J]. 中国实验方剂学杂志, 2020,26(9):23-28. DOI： 10.13422/j.cnki.syfjx.20200603.

Yan TANG, Yan CHENG, Xiao-yu JING, et al. Effect of Longmu Guizhi Decoction and Its Disassembled Prescription on Hypothalamic-Pituitary-Adrenal Axis in Rats with Attention Deficit Hyperactivity Disorder[J]. Chinese Journal of Experimental Traditional Medical Formulae, 2020,26(9):23-28. DOI： 10.13422/j.cnki.syfjx.20200603.

摘要

目的：

探讨龙牡桂枝汤及其拆方对注意缺陷多动障碍(ADHD)动物模型—自发性高血压大鼠(SHR)下丘脑-垂体-肾上腺轴(HPA)的调节作用，阐释复方配伍的科学内涵。

方法：

幼年雄性SHR大鼠随机分为生理盐水组，盐酸哌甲酯组(2 mg·kg

-1

)，龙牡桂枝汤组(30 g·kg

-1

)，桂枝加龙骨牡蛎汤组(21 g·kg

-1

)，甘麦大枣汤组(9.24 g·kg

-1

)，石菖蒲-远志组(4.62 g·kg

-1

)，分别予相应药物灌胃14 d，采用酶联免疫吸附测定法(ELISA)检测大鼠血清促肾上腺皮质激素释放激素(CRH)，促肾上腺皮质激素(ACTH)，皮质酮(CORT)的含量，实时荧光定量聚合酶链式反应(Real-time PCR)检测下丘脑盐皮质激素受体(MR)，糖皮质激素受体(GR)，CRH及海马GR，MR mRNA的表达水平。

结果：

与生理盐水组比较，盐酸哌甲酯组、龙牡桂枝汤组大鼠血清CORT，ACTH，CRH水平，下丘脑GR，CRH及海马MR，GR mRNA的表达水平明显升高(

0.05，

0.01)，其海马GR mRNA表达明显高于盐酸哌甲酯组(

0.01)。拆方研究显示：与生理盐水组比较，桂枝加龙骨牡蛎汤组和甘麦大枣汤组大鼠血清ACTH，CRH水平，下丘脑MR，GR，CRH及海马GR，MR mRNA的表达明显升高(

0.05，

0.01)，桂枝加龙骨牡蛎汤组大鼠血清CORT水平明显升高(

0.01)，石菖蒲-远志组大鼠血清ACTH水平明显升高(

0.05)。

结论：

龙牡桂枝汤治疗ADHD的作用机制与提高血清CORT，ACTH，CRH水平，增加下丘脑MR，GR，CRH及海马GR，MR mRNA的表达，从而调控HPA轴功能有关。各拆方药组对HPA轴功能的影响程度依次为桂枝加龙骨牡蛎汤>甘麦大枣汤>石菖蒲-远志。

Abstract

Objective:

To explore the regulatory effect of Longmu Guizhi decoction and its decomposed formula on the hypothalamic-pituitary-adrenal axis of spontsneously hyoertensive rats (SHR) with attention deficit hyperactivity disorder (ADHD)

so as to explain the scientific connotation of compound compatibility.

Method:

Young male SHR rats were randomly divided into saline control group

methylphenidate hydrochloride group(2 mg·kg

-1

)

Longmu Guizhi decoction group(30 g·kg

-1

)

Guizhi+ Longgu Muli decoction group(21 g·kg

-1

)

Ganmai Dazaotang group(9.24 g·kg

-1

) and Polygalae Radix-Acori Tatarinowii Rhizome group(4.62 g·kg

-1

). The corresponding drugs were intragastrically administered for 14 days. Serum adrenocorticotropic hormone (CRH)

adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were detected by enzyme-linked immunosorbent assay(ELISA)

and mRNA expressions of glucocorticoid receptor (GR)

mineralocorticoid receptor (MR)

CRH in hypothalamus and GR

MR in hippocampus were detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) method.

Result:

Serum CORT

ACTH and CRH

GR and CRH mRNA expressions of hypothalamus

GR and MR mRNA expressions of hippocampus in methylphenidate hydrochloride group and Longmu Guizhi decoction group were significantly higher than those of saline control group (

0.05

0.01). MR mRNA expression of hypothalamus in Longmu Guizhi decoction group was significantly higher than that in the saline control group (

0.05

0.01)

and GR expression in hippocampus was significantly higher than that in the methylphenidate hydrochloride group (

0.01). The dissection study showed that the levels of serum ACTH and CRH

MR mRNA

GR and CRH mRNA of hypothalamus

GR and MR mRNA of hippocampus in Guizhi+ Longgu Muli decoction group and Ganmai Dazaotang group were significantly higher than those in saline control group (

0.05

0.01). The serum CORT level of Guizhi+ Longgu Muli decoction group was higher than that of normal saline group (

0.01). The serum ACTH level of Polygalae Radix-Acori Tatarinowii Rhizome pair was significantly higher than that in saline control group(

0.05).

Conclusion:

The mechanism of Longmu Guizhi decoction in treating ADHD is related to increase of the levels of CORT

ACTH and CRH in serum and the expressions of MR

CRH in hypothalamus and GR and MR in hippocampus

so as to regulate the function of HPA axis. The order of the effect degree of each decomposition group on HPA axis function from high to low was Guizhi+ Longgu Muli decoction>Ganmai Dazao decoction>Polygalae Radix-Acori Tatarinowii Rhizome pair drug.

关键词

注意缺陷多动障碍龙牡桂枝汤拆方下丘脑-垂体-肾上腺轴

Keywords

attention deficit hyperactivity disorder (ADHD)Longmu Guizhi decoctiondisassembled prescriptionhypothalamic pituitary gonadal axis

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