Effects of Modified<italic style="font-style: italic"> Xiaoyao Powder</italic> （逍遥散） on the Programmed Cell Death of Hypothalamic Dopaminergic Neurons in Rat Model of Hyperprolactinemia with Liver Depression and Spleen Deficiency

LI Yan; LI Yan; LIU Kaixin; DAI Kangli; LIU Xiao; Yang Hui; Luo Dan

doi:10.13288/j.11-2166/r.2024.03.015

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Effects of Modified Xiaoyao Powder （逍遥散） on the Programmed Cell Death of Hypothalamic Dopaminergic Neurons in Rat Model of Hyperprolactinemia with Liver Depression and Spleen Deficiency

更新时间：2024-01-25

- Effects of Modified Xiaoyao Powder （逍遥散） on the Programmed Cell Death of Hypothalamic Dopaminergic Neurons in Rat Model of Hyperprolactinemia with Liver Depression and Spleen Deficiency
- Journal of Traditional Chinese Medicine Vol. 65, Issue 3, Pages: 317-323(2024)
- 作者机构：
  
  贵州中医药大学，贵州省贵阳市南明区市东路50号，550001
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2024.03.015
  CLC：
- Received：20 August 2023，
  
  Revised：2023-11-09，
  
  Published：02 February 2024
- 稿件说明：
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李燕,李燕,刘凯鑫等.逍遥散加减方对高催乳素血症肝郁脾虚型模型大鼠下丘脑多巴胺能神经元细胞程序性坏死的影响[J].中医杂志,2024,65(03):317-323.

LI Yan,LI Yan,LIU Kaixin,et al.Effects of Modified Xiaoyao Powder （逍遥散） on the Programmed Cell Death of Hypothalamic Dopaminergic Neurons in Rat Model of Hyperprolactinemia with Liver Depression and Spleen Deficiency[J].Journal of Traditional Chinese Medicine,2024,65(03):317-323.
李燕,李燕,刘凯鑫等.逍遥散加减方对高催乳素血症肝郁脾虚型模型大鼠下丘脑多巴胺能神经元细胞程序性坏死的影响[J].中医杂志,2024,65(03):317-323. DOI： 10.13288/j.11-2166/r.2024.03.015.

LI Yan,LI Yan,LIU Kaixin,et al.Effects of Modified Xiaoyao Powder （逍遥散） on the Programmed Cell Death of Hypothalamic Dopaminergic Neurons in Rat Model of Hyperprolactinemia with Liver Depression and Spleen Deficiency[J].Journal of Traditional Chinese Medicine,2024,65(03):317-323. DOI： 10.13288/j.11-2166/r.2024.03.015.

摘要

目的

探讨逍遥散加减方治疗肝郁脾虚型高催乳素血症（HPRL）的可能作用机制。

方法

96只SD雌性大鼠随机分为正常组16只，造模组80只。造模组大鼠采用慢性不可预知应激联合甲氧氯普胺腹腔注射构建HPRL肝郁脾虚型模型大鼠。将80只造模成功的大鼠随机分为模型组，逍遥散加减方高、中、低剂量组和甲磺酸溴隐亭组，每组16只。逍遥散加减方高、中、低剂量组分别给予逍遥散加减方60、30、15 g/（kg·d）灌胃，甲磺酸溴隐亭组予以甲磺酸溴隐亭片1 mg/（kg·d）灌胃，正常组及模型组给予生理盐水10 ml/（kg·d）灌胃，连续给药14天。ELISA法检测血清催乳素（PRL）含量；免疫组化测定大鼠下丘脑肿瘤坏死因子α（TNF-α）和酪氨酸羟化酶（TH）表达；采用Western blot法检测下丘脑肿瘤坏死因子受体1（TNFR1）蛋白表达；RT-PCR法检测下丘脑受体相互作用蛋白激酶3（RIP3）mRNA表达；免疫荧光法检测RIP3和多巴胺能神经元的共表达情况。

结果

与正常组比较，模型组血清PRL含量升高，下丘脑TNF-α、TNFR1、RIP3 mRNA及RIP3与多巴胺能神经元共表达阳性细胞数显著升高，TH表达降低（

＜0.05或

＜0.01）；与模型组比较，甲磺酸溴隐亭组和逍遥散加减方低剂量组下丘脑TNF-α表达降低，甲磺酸溴隐亭组和逍遥散加减方中、高剂量组TH表达显著升高，逍遥散加减方各剂量组和甲磺酸溴隐亭组血清PRL含量，下丘脑TNFR1、RIP3 mRNA，RIP3与多巴胺能神经元共表达阳性细胞数均显著降低（

＜0.05或

＜0.01）；与甲磺酸溴隐亭组比较，逍遥散加减方高、低剂量组血清PRL含量显著升高，逍遥散加减方中剂量组TH表达显著升高，逍遥散加减方低剂量组下丘脑RIP3 mRNA表达降低，逍遥散加减方高剂量组RIP3与多巴胺能神经元共表达阳性细胞数显著升高（

＜0.01）。

结论

逍遥散加减方可调节下丘脑多巴胺能神经元细胞程序性坏死，影响DA表达，从而调节PRL水平，可能是其治疗HPRL肝郁脾虚型的机制之一。

Abstract

Objective

To investigate the possible mechanisms of modified

Xiaoyao Powder

（逍遥散） in the treatment of hyperprolactinemia （HPRL） with liver constraint and spleen deficiency.

Methods

Ninety-six female SD rats were randomly divided into a normal group （n=16） and a modeling group （n=80）. In the modeling group， rats were subjected to chronic unpredictable stress combined with intraperitoneal injection of metoclopramide to establish a rat model of HPRL with liver constraint and spleen deficiency. The 80 successfully modeled rats were randomly divided into a model group， a high， medium， and low-dose group of modified

Xiaoyao Powder，

and a bromocriptine group， with 16 rats in each group. The high， medium， and low-dose groups of modified

Xiaoyao Powder

were orally administered doses of 60， 30， and 15 g/（kg·d） respectively， the bromocriptine group was orally administered bromocriptine tablets at a dose of 1 mg/（kg·d）， and the normal group and model group were orally administered 10 ml/（kg·d） of normal saline for 14 consecutive days. ELISA was used to detect serum prolactin （PRL） level； immunohistochemistry was used to determine the expression of tumor necrosis factor-alpha （TNF-α） and tyrosine hydroxylase （TH） in the hypothalamus； Western blot was used to detect the protein expression of tumor necrosis factor receptor 1 （TNFR1） in the hypothalamus； Real-time PCR was used to detect the mRNA expression of receptor interacting protein kinase 3 （RIP3） in the hypothalamus； immunofluorescence was used to detect the co-expression of RIP3 and dopamine neurons in the hypothalamus.

Results

Compared with the normal group， the serum PRL levels were increased in the model group， and the expression of hypothalamic TNF-α， TNFR1， RIP3 mRNA， and the co-expression of RIP3 with dopamine neurons were significantly increased， while TH expression was decreased （

＜0.05 or

＜0.01）. Compared with the model group， the expression of hypothalamic TNF-α was decreased in the bromocriptine group and low-dose group of modified

Xiaoyao Powder

， and the expression of TH was significantly increased in the medium and high-dose groups of modified

Xiaoyao Powder

and the bromocriptine group. The serum PRL levels， hypothalamic TNFR1 and RIP3 mRNA expression， and the co-expression of RIP3 with dopamine neurons were significantly decreased in all dose groups of modified

Xiaoyao Powder

and the bromocriptine group （

＜0.05 or

＜0.01）. Compared with the bromocriptine group， the serum PRL level were significantly increased in the high and low-dose groups of modified

Xiaoyao Powder

， TH expression was significantly increased in the medium-dose group of modified

Xiaoyao Powder

， hypothalamic RIP3 mRNA expression was decreased in the low-dose group of modified

Xiaoyao Powder

， and the co-expression of RIP3 with dopamine neurons was significantly increased in the high-dose group of modified

Xiaoyao Powder

（

＜0.01）.

Conclusion

Modified

Xiaoyao Powder

can regulate the programmed cell death of hypothalamic dopamine neurons， affect DA expression， and regulate PRL levels， which may be one of its mechanisms in the treatment of HPRL with liver constraint and spleen deficiency.

关键词

Keywords

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Heilongjiang University of Chinese Medicine

The Academy of Military Medical Sciences of the People's Liberation Army Academy of Military Sciences

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Department of Traditional Chinese Medicine，The Sixth Medical Centre，The People's Liberation Army General Hospital

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Effects of Modified Xiaoyao Powder （逍遥散） on the Programmed Cell Death of Hypothalamic Dopaminergic Neurons in Rat Model of Hyperprolactinemia with Liver Depression and Spleen Deficiency

DOI：10.13288/j.11-2166/r.2024.03.015

摘要

Abstract

关键词

Keywords

references