Effects of <italic style="font-style: italic">Gengxin Decoction</italic> （更欣汤） on Oestrogen Receptors and Orexin A in the Nucleus Accumbens of the Hypothalamus Nodularis Papillaris in Perimenopausal Insomnia Model Mice

LI Xiuheng; TANG Ling; SUN Tianlin; SUN Xiaohui

doi:10.13288/j.11-2166/r.2024.23.013

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Effects of Gengxin Decoction （更欣汤） on Oestrogen Receptors and Orexin A in the Nucleus Accumbens of the Hypothalamus Nodularis Papillaris in Perimenopausal Insomnia Model Mice

更新时间：2024-11-25

- Effects of Gengxin Decoction （更欣汤） on Oestrogen Receptors and Orexin A in the Nucleus Accumbens of the Hypothalamus Nodularis Papillaris in Perimenopausal Insomnia Model Mice
- Journal of Traditional Chinese Medicine Vol. 65, Issue 23, Pages: 2461-2467(2024)
- 作者机构：
  
  1.北京中医药大学东直门医院，北京市东城区海运仓5号，100700
  2.北京中医药大学第三附属医院
  3.北京市第一中西医结合医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2024.23.013
  CLC：
- Received：26 May 2024，
  
  Revised：2024-08-30，
  
  Published：02 December 2024
- 稿件说明：
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李修恒,汤玲,孙天琳等.更欣汤对围绝经期失眠模型小鼠下丘脑结节状乳头体核雌激素受体和食欲素A的影响[J].中医杂志,2024,65(23):2461-2467.

LI Xiuheng,TANG Ling,SUN Tianlin,et al.Effects of Gengxin Decoction （更欣汤） on Oestrogen Receptors and Orexin A in the Nucleus Accumbens of the Hypothalamus Nodularis Papillaris in Perimenopausal Insomnia Model Mice[J].Journal of Traditional Chinese Medicine,2024,65(23):2461-2467.
李修恒,汤玲,孙天琳等.更欣汤对围绝经期失眠模型小鼠下丘脑结节状乳头体核雌激素受体和食欲素A的影响[J].中医杂志,2024,65(23):2461-2467. DOI： 10.13288/j.11-2166/r.2024.23.013.

LI Xiuheng,TANG Ling,SUN Tianlin,et al.Effects of Gengxin Decoction （更欣汤） on Oestrogen Receptors and Orexin A in the Nucleus Accumbens of the Hypothalamus Nodularis Papillaris in Perimenopausal Insomnia Model Mice[J].Journal of Traditional Chinese Medicine,2024,65(23):2461-2467. DOI： 10.13288/j.11-2166/r.2024.23.013.

摘要

目的

从下丘脑结节状乳头体核（TMN）雌激素受体和食欲素A（OXA）表达的角度探究更欣汤治疗围绝经期失眠的可能作用机制。

方法

选取动情周期规律的雌性ICR小鼠，应用4-乙烯基环己烯二环氧化物（VCD）联合对氯苯丙氨酸（PCPA）混悬液腹腔注射建立围绝经期失眠小鼠模型。造模成功的75只小鼠随机分为模型组、佐必克隆组及更欣汤低、中、高剂量组，每组15只，另设正常小鼠15只为空白组。造模成功后次日，更欣汤低、中、高剂量组小鼠每日9：00分别给予更新汤颗粒1.15、2.3、4.6 g·kg

-1

·d

-1

灌胃，佐匹克隆组小鼠同时间点给予佐匹克隆混悬液1.13 mg·kg

-1

·d

-1

灌胃，空白组、模型组小鼠同时间点予蒸馏水1 ml·kg

-1

·d

-1

灌胃，各组均连续14天。实验期间观察各组小鼠日间活动、精神状态、饮食、毛色等一般情况；末次干预24 h后，采用戊巴比妥钠协同试验检测小鼠睡眠潜伏期及睡眠持续期，ELISA法检测小鼠血清雌二醇（E

）、孕酮（P）、促卵泡生成激素（FSH）以及下丘脑TMN区OXA水平，免疫荧光染色法检测小鼠TMN区雌激素受体α（ERα）、OXA、雌激素受体β（ERβ）蛋白光密度值。

结果

空白组小鼠昼夜节律正常；模型组小鼠昼夜节律紊乱，白天和晚上保持活跃；更欣汤各组小鼠精神状态较前改善，小鼠精神状态明显好转，白天活动较前减少，毛色稍黄、但有光泽，尤以更欣汤中剂量组最明显；佐匹克隆组白天活动较前减少，毛发粗糙少光泽，警觉性高。与空白组比较，模型组小鼠睡眠潜伏期延长，睡眠持续期缩短，血清E

、P水平降低，血清FSH和TMN区OXA蛋白表达增加，TMN区ERα、ERβ光密度值减少，OXA光密度值增加（

＜0.05或

＜0.01）。与模型组比较，更欣汤低、中、高剂量组和佐匹克隆组小鼠睡眠潜伏期缩短，睡眠持续期延长（

＜0.01）；更欣汤中、高剂量组血清E

、P水平升高，FSH及TMN区OXA水平降低（

＜0.05）；更欣汤中剂量组小鼠TMN区ERα光密度值增加，更欣汤低、中剂量组和佐匹克隆组OXA光密度值减少，更欣汤低、中、高剂量组和佐匹克隆组小鼠TMN区ERβ光密度值增加（

＜0.05）。与佐匹克隆组比较，更欣汤低剂量组小鼠睡眠潜伏期时间延长、睡眠持续时间缩短，更欣汤中、高剂量组血清E

水平及TMN区ERβ光密度值升高、血清FSH及TMN区OXA水平降低（

＜0

.05）。与更欣汤低剂量组比较，更欣汤中、高剂量组小鼠睡眠潜伏期缩短，血清FSH水平降低（

＜0.01）。

结论

更欣汤可能通过调控TMN区雌激素受体和OXA分布，抑制TMN区食欲素系统过度激活，从而抑制觉醒、改善围绝经期失眠。

Abstract

Objective

To explore the possible mechanism of

Gengxin Decoction

（更欣汤） in the treatment of perimenopausal insomnia from the perspective of the expression of oestrogen receptor and orexin A （OXA） in hypothalamic tuberomammillary nucleus （TMN）.

Methods

Female ICR mice with regular estrous cycle were selected to establish perimenopausal insomnia mice models by injecting 4-vinylcyclohexene diepoxide （VCD） combined with para-chlorophenylalanine （PCPA） suspension intraperitoneally. After successful modeling， 75 mice models were randomly divided into model group， zopiclone group and low-， middle-， and high-dose

Gengxin Decoction

， with 15 mice in each group， and 15 normal mice were set as blank group. On the next day after successful modelling， mice in the low-， middle-， and high-dose

Gengxin Decoction

were given

Gengxin Decoction

granules 1.15， 2.3 and 4.6 g·kg

-1

·d

-1

by gavage at 9：00 AM every day， mice in the zopiclone group were given zopiclone suspension 1.13 mg·kg

-1

·d

-1

by gavage at the same time point， and mice in the blank and model groups were given distilled water 1 ml·kg

-1

·d

-1

by gavage at the same time point， for 14 days in all groups. During the experimental period， general conditions of the mice in each group， such as daytime activities， mental state， diet and coat colour， were observed； twenty-four hours after the final intervention， the sleep latency and sleep duration of mice were detected by sodium pentobarbital synergy test， and the levels of serum estradiol （E

）、progesterone （P）、follicle stimulating hormone （FSH） and OXA protein in TMN of hypothalamus were detected by ELIS

A， and the protein optical density values of estrogen receptor α （ERα）， OXA and ERβ in TMN was detected by immunofluorescence staining.

Results

The circadian rhythm of mice was regular in the blank group； the circadian rhythm of mice was disordered in the model group， and they remained active during the day and night； the mental state of mice in each group of

Gengxin Decoction

was improved compared with that before， which showed that the daytime activity was less than before， and the coat color was slightly yellow but shiny， and the mental state of mice was significantly improved in the middle-dose

Gengxin Decoction

； the zopiclone group was less active during the day than before， had rough， less shiny hair， and was more alert. Compared with the blank group， the sleep latency of mice in the model group prolonged， the sleep duration shortened， serum E

and P decreased， serum FSH and the expression of OXA protein in TMN region increased， the optical density of ERα and ERβ in TMN region decreased， and the optical density of OXA increased （

＜0.05 or

＜0.01）. Compared with the model group， the sleep latency of the mice in the low-， middle-， and high-dose

Gengxin Decoction

groups and the zopiclone group shortened， the sleep duration prolonged （

＜0.01）； the serum E

and P in the middle-， and high-dose

Gengxin Decoction

groups increased， FSH and the expression of OXA protein in TMN area decreased （

＜0.05）； the optical density values of ERα in TMN area increased in the medium-dose group， and the optical density value of OXA decreased in low- and middle-dose

Gengxin Decoction

groups， and the optical density values of ERβ in TMN area increased in low-， middle-， and high-dose

Gengxin Decoction

groups and the zopiclone group （

＜0.05 ）. Compared with the zopiclone group， mice in the low-dose

Gengxin Decoction

group had longer sleep latency and shorter sleep duration， and mice in the middle- and high-dose

Gengxin Decoction

groups had higher serum E

level and ERβ optical density value in the TMN area， and lower serum FSH and OXA level in the TMN area （

＜0.05）. Compared with the low-dose

Gengxin Decoction

group， the sleep latency of mice in the middle- and high-dose

Gengxin Decoction

groups shortened， and the serum FSH level reduced （

＜0.01）.

Conclusion

Gengxin Decoction

may inhibit arousal and improve perimenopausal insomnia by modulating the distribution of estrogen receptors and OXA in the TMN region， and inhibiting the overactivation of the orexin system in the TMN region.

关键词

Keywords

references

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Dongzhimen Hospital，Beijing University of Chinese Medicine

Wangjing Hospital， China Academy of Chinese Medical Science

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Effects of Gengxin Decoction （更欣汤） on Oestrogen Receptors and Orexin A in the Nucleus Accumbens of the Hypothalamus Nodularis Papillaris in Perimenopausal Insomnia Model Mice

DOI：10.13288/j.11-2166/r.2024.23.013

摘要

Abstract

关键词

Keywords

references