Effect of <italic style="font-style: italic">Geng Xin Decoction</italic> （更欣汤） on Hypothalamic Biological Clock Gene Expression in Perimenopausal Insomnia Model Rats

WANG Yixuan; TANG Ling; SUN Tianlin; SHI Meiying; LU Yiqin; LI Xiuheng

doi:10.13288/j.11-2166/r.2023.08.014

您当前的位置：

首页 >

文章列表页 >

Effect of Geng Xin Decoction （更欣汤） on Hypothalamic Biological Clock Gene Expression in Perimenopausal Insomnia Model Rats

更新时间：2023-04-14

- Effect of Geng Xin Decoction （更欣汤） on Hypothalamic Biological Clock Gene Expression in Perimenopausal Insomnia Model Rats
- Journal of Traditional Chinese Medicine Vol. 64, Issue 8, Pages: 835-840(2023)
- 作者机构：
  
  1.成都中医药大学，四川省成都市金牛区十二桥路37号，610032
  2.北京中医药大学东直门医院
  3.北京市第一中西医结合医院
  4.中国中医科学院望京医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2023.08.014
  CLC：
- Received：07 July 2022，
  
  Revised：2023-02-16，
  
  Published：17 April 2023
- 稿件说明：
移动端阅览
王艺璇,汤玲,孙天琳等.更欣汤对围绝经期失眠模型大鼠下丘脑生物钟基因表达的影响[J].中医杂志,2023,64(08):835-840.

WANG Yixuan,TANG Ling,SUN Tianlin,et al.Effect of Geng Xin Decoction （更欣汤） on Hypothalamic Biological Clock Gene Expression in Perimenopausal Insomnia Model Rats[J].Journal of Traditional Chinese Medicine,2023,64(08):835-840.
王艺璇,汤玲,孙天琳等.更欣汤对围绝经期失眠模型大鼠下丘脑生物钟基因表达的影响[J].中医杂志,2023,64(08):835-840. DOI： 10.13288/j.11-2166/r.2023.08.014.

WANG Yixuan,TANG Ling,SUN Tianlin,et al.Effect of Geng Xin Decoction （更欣汤） on Hypothalamic Biological Clock Gene Expression in Perimenopausal Insomnia Model Rats[J].Journal of Traditional Chinese Medicine,2023,64(08):835-840. DOI： 10.13288/j.11-2166/r.2023.08.014.

摘要

目的

探讨更欣汤治疗围绝经期失眠的可能作用机制。

方法

60只SD雌性大鼠筛选出动情周期规律的大鼠52只，随机分为空白组13只和造模组39只。造模组大鼠采用雷公藤多苷片灌胃联合对氯苯丙氨酸（PCPA）混悬液腹腔注射建立围绝经期失眠大鼠模型。将26只造模成功的大鼠随机分为模型组和更欣汤组各13只。更欣汤组每日予更欣汤颗粒剂1.8 g/（kg·d）灌胃，空白组和模型组大鼠每日予10 ml/（kg·d）生理盐水灌胃，连续14天。观察大鼠一般行为学变化，采用戊巴比妥钠协同实验检测大鼠睡眠情况（睡眠潜伏期、睡眠持续期），采用Western blot法检测大鼠下丘脑生物钟基因CLOCK、芳基烃受体核转运体样蛋白（BMAL1）、Per1、Per2蛋白表达，RT-qPCR法检测大鼠下丘脑CLOCK、BMAL1、Per1、Per2 mRNA表达。

结果

戊巴比妥钠协同实验结果显示，模型组和更欣汤组大鼠睡眠持续期较空白组延长（

＜0.05），各组大鼠睡眠潜伏期差异均无统计学意义（

＞0.05）。与空白组比较，模型组大鼠精神状态差，前期白天及夜间均活跃、呈觉醒状态，摄食水减少，毛发竖起、色淡黄、色泽干枯、易脱落，大便呈黄绿色、质软或质稀不成形；下丘脑CLOCK、BMAL1蛋白表达水平升高，Per1、Per2蛋白表达水平降低（

＜0.05或

＜0.01）。与模型组比较，更欣汤组大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，大便成形，下丘脑Per2蛋白表达水平升高（

＜0.01），CLOCK、BMAL1及Per1蛋白表达水平均无统计学意义（

＞0.05）。各组大鼠下丘脑CLOCK、BMAL1、Per1、Per2 mRNA相对表达量比较差异均无统计学意义（

＞0.05）。

结论

更欣汤可改善围绝经期失眠模型大鼠睡眠状态，其作用机制可能与上调下丘脑生物钟基因Per2蛋白表达有关。

Abstract

Objective

To explore the possible mechanism of

Geng Xin Decoction

（更欣汤， GXD） in treating perimenopausal insomnia.

Methods

Fifty-two out of 60 SD female rats with regular estrous cycle were selected and randomly divided intoblank group （n=13） and modeling group （n=39）. The rats in the modeling group were given tripterygium glycosides by gavage and intraperitoneal injection of p-chlorophenylalanine （PCPA） suspension to establish the perimenopausal insomnia rat model. Twenty-six successfully modeled rats were randomly divided into a model group and GXD group with 13 rats in each group. Rats in the GXD group were given 1.8 g/（kg·d） of

Geng Xin Decoction

granules by gavage every day， while those in the blank group and model group were given 10 ml/（kg·d） of normal saline by gavage every day， all for 14 days. The general behavioral changes of rats were observed. Pentobarbital sodium synergistic experiment was applied to detect the sleep status of the rats including sleep latency and sleep duration. Western blotting was used to detect the protein expression of biological clock gene CLOCK， BMAL1， Per1， and Per2 in the hypothalamus， and RT-qPCR method was used to detect the mRNA expression of CLOCK， BMAL1， Per1， and Per2.

Results

The results of pentobarbital sodium synergistic experiment showed that the sleep duration was prolonged in the model group and GXD group than in the blank group （

＜0.05）， while no significant difference was found among the three groups in the sleep latency （

＞0.05）. Compared to those in the blank group， the rats in the model group were in poor mental state and were active both in the daytime and at night in the early stage， showing an arousal state with decreased food and water intake， hair erection with light yellow， dry， and easy to fall off hair； the stool was yellow-green， soft or thin； the protein expression level of CLOCK and BMAL1 in hypothalamus increased， while the protein expression level of Per1 and Per2 decreased （

＜0.05 or

＜0.01）. Compared to those in the model group， the mental state of the rats in GXD group was significantly improved， and the daytime activities of the rats decreased， with slightly yellow but shiny hair， and formed stool； the protein expression level of Per2 increased， while that of CLOCK， BMAL1 and Per1 protein was not statistically significant （

＞0.05）. There was no significant difference in the relative mRNA expression of CLOCK， BMAL1， Per1 and Per2 in the hypothalamus among the groups （

＞0.05）.

Conclusion

The mechanism of GXD in improving the sleep state of perimenopausal insomnia rats may be related to the up-regulation of protein expression of the biological clock gene Per2 in the hypothalamus.

关键词

Keywords

references

PROSERPIO P ， MARRA S ， CAMPANA C ， et al . Insomnia and menopause： a narrative review on mechanisms and treatments ［J］. Climacteric ， 2020 ， 23 （ 6 ）： 539 - 549 .

TANDON VR ， SHARMA S ， MAHAJAN A ， et al . Menopause and sleep disorders ［J］. J Midlife Health ， 2022 ， 13 （ 1 ）： 26 - 33 .

HATCHER KM ， ROYSTON SE ， MAHONEY MM . Modulation of circadian rhythms through estrogen receptor signaling ［J］. Eur J Neurosci ， 2020 ， 51 （ 1 ）： 217 - 228 .

BAILEY M ， SILVER R . Sex differences in circadian timing systems： implications for disease ［J］. Front Neuroendocrinol ， 2014 ， 35 （ 1 ）： 111 - 139 .

QUINTELA T ， ALBUQUERQUE T ， LUNDKVIST G ， et al . The choroid plexus harbors a circadian oscillator modulated by estrogens ［J］. Chronobiol Int ， 2018 ， 35 （ 2 ）： 270 - 279 .

贾林娜 . 更欣汤治疗女性更年期失眠症（心肾不交型）的临床疗效评价［D］. 北京：北京中医药大学， 2021 .

印丹丹，封瑞，任丽菲，等 . 阴道涂片法鉴定大鼠生理周期的应用评价［J］. 解剖科学进展， 2014 ， 20 （ 4 ）： 360 - 363 .

张婷，王颖，王莉 . 大鼠阴道涂片两种染色方法比较［J］. 中国比较医学杂志， 2018 ， 28 （ 12 ）： 98 - 101 .

杨溢铎，李佶 . 围绝经期动物模型建立方法的研究进展［J］. 医学研究杂志， 2019 ， 48 （ 6 ）： 176 - 180 .

刘晓宇，王娇，钱欣，等 . 围绝经期大鼠动情周期变化的研究［J］. 哈尔滨医科大学学报， 2014 ， 48 （ 5 ）： 358 - 360 .

肖成荣，马增春，李海静，等 . PCPA失眠大鼠模型的制作及其机制［J］. 毒理学杂志， 2007 ， 21 （ 4 ）： 326 .

徐叔云 . 药理实验方法学［M］. 北京：人民卫生出版社， 2002 ： 203 .

叶钰娟，李昕蓉，曹梦琪，等 . 中医失眠证候模型的研究述评［J］. 中国中医基础医学杂志， 2021 ， 27 （ 1 ）： 178 - 181 .

COX KH ， TAKAHASHI JS . Circadian clock genes and the transcriptional architecture of the clock mechanism ［J］. J Mol Endocrinol ， 2019 ， 63 （ 4 ）： R93 - R102 .

KONDRATOVA AA ， KONDRATOV RV . The circadian clock and pathology of the ageing brain ［J］. Nat Rev Neurosci ， 2012 ， 13 （ 5 ）： 325 - 335 .

魏文静，仝立国，仲启明，等 . 生物钟基因与睡眠障碍的研究进展［J］. 实用医药杂志， 2018 ， 35 （ 5 ）： 455 - 457 .

KOIKE N ， YOO SH ， HUANG HC ， et al . Transcriptional architecture and chromatin landscape of the core circadian clock in mammals ［J］. Science ， 2012 ， 338 （ 6105 ）： 349 - 354 .

MONTI JM ， JANTOS H . The roles of dopamine and serotonin， and of their receptors， in regulating sleep and waking ［J］. Prog Brain Res ， 2008 ， 172 （ 1 ）： 625 - 646 .

肖迪，刘俊，郑桃云 . 交泰丸对睡眠剥夺小鼠视交叉上核生物钟基因Clock及Bmal 1表达的影响［J］. 湖北中医药大学学报， 2019 ， 21 （ 4 ）： 25 - 29 .

魏文静，仝立国，仲启明，等 . 蛇床子催眠活性组分对对氯苯丙氨酸致失眠大鼠海马钟基因与氨基酸类神经递质表达的影响［J］. 中草药， 2018 ， 49 （ 11 ）： 2614 - 2619 .

查看原文

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Treatment of Chronic Insomnia Based on the Theory that "Spleen Fuctions as Wei Qi"：An Approach from the "Gut Microbiota-Circadian Rhythm-Ying-Wei Circulation" Perspective

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

Effects of Hewei Anshe Formula （和胃安神方） on the CLOCK and BMAL1 Gene Expression of Hypothalamic Biological Clock in Insomnia Rat Models

Chronotherapy Strategy for Irritable Bowel Syndrome in Traditional Chinese Medicine Chronomedicine

ZHANG Zhiyuan's Experience in Treating Perimenopause-Related Insomnia with the Method of Regulating the Heart and Governing the Spirit

Related Author

GAO Yu

WANG Meng

LI Yuxi

SU Zhiying

ZHANG Xiaoxuan

YUAN Jiamin

XU Biyun

YANG Zhimin

Related Institution

The Second Clinical Medical College of Guangzhou University of Chinese Medicine

The Second Affiliated Hospital of Guangzhou University of Chinese Medicine

Dongzhimen Hospital，Beijing University of Chinese Medicine

Beijing University of Chinese Medicine Third Affiliated Hospital

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

Address：No.16, Nanxiao street, Dongzhimen, Dongcheng District, Beijing Postal code：100700
Tel：010-64035632 Email：jtcmcn@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备09064830号-19 京公网安备11010102007558号
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰

Effect of Geng Xin Decoction （更欣汤） on Hypothalamic Biological Clock Gene Expression in Perimenopausal Insomnia Model Rats

DOI：10.13288/j.11-2166/r.2023.08.014

摘要

Abstract

关键词

Keywords

references