Effects of Modified <italic style="font-style: italic">Shoutai Pill </italic>（寿胎丸） on Endoplasmic Reticulum Stress and Decidualization in the Endometrium for Hyperandrogenism and Insulin Resistance-Induced Fetal Loss of Rats with Polycystic Ovary Syndrome

GUO Tingting; JIANG Meng; HAN Jing; GUO Xiaozhu; ZHANG Yuehui

doi:10.13288/j.11-2166/r.2025.17.011

您当前的位置：

首页 >

文章列表页 >

Effects of Modified Shoutai Pill （寿胎丸） on Endoplasmic Reticulum Stress and Decidualization in the Endometrium for Hyperandrogenism and Insulin Resistance-Induced Fetal Loss of Rats with Polycystic Ovary Syndrome

更新时间：2025-08-28

- Effects of Modified Shoutai Pill （寿胎丸） on Endoplasmic Reticulum Stress and Decidualization in the Endometrium for Hyperandrogenism and Insulin Resistance-Induced Fetal Loss of Rats with Polycystic Ovary Syndrome
- Journal of Traditional Chinese Medicine Vol. 66, Issue 17, Pages: 1801-1809(2025)
- 作者机构：
  
  1.黑龙江中医药大学，黑龙江省哈尔滨市香坊区和平路24号，150040
  2.黑龙江省中医药科学院
  3.黑龙江中医药大学附属第一医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2025.17.011
  CLC：
- Received：04 December 2024，
  
  Revised：2025-04-29，
  
  Published：02 September 2025
- 稿件说明：
移动端阅览
郭婷婷,蒋蒙,韩静等.寿胎丸加味方对多囊卵巢综合征高雄激素-胰岛素抵抗流产模型大鼠子宫内膜内质网应激和蜕膜化的影响[J].中医杂志,2025,66(17):1801-1809.

GUO Tingting,JIANG Meng,HAN Jing,et al.Effects of Modified Shoutai Pill （寿胎丸） on Endoplasmic Reticulum Stress and Decidualization in the Endometrium for Hyperandrogenism and Insulin Resistance-Induced Fetal Loss of Rats with Polycystic Ovary Syndrome[J].Journal of Traditional Chinese Medicine,2025,66(17):1801-1809.
郭婷婷,蒋蒙,韩静等.寿胎丸加味方对多囊卵巢综合征高雄激素-胰岛素抵抗流产模型大鼠子宫内膜内质网应激和蜕膜化的影响[J].中医杂志,2025,66(17):1801-1809. DOI： 10.13288/j.11-2166/r.2025.17.011.

GUO Tingting,JIANG Meng,HAN Jing,et al.Effects of Modified Shoutai Pill （寿胎丸） on Endoplasmic Reticulum Stress and Decidualization in the Endometrium for Hyperandrogenism and Insulin Resistance-Induced Fetal Loss of Rats with Polycystic Ovary Syndrome[J].Journal of Traditional Chinese Medicine,2025,66(17):1801-1809. DOI： 10.13288/j.11-2166/r.2025.17.011.

摘要

目的

探讨寿胎丸加味方治疗多囊卵巢综合征（PCOS）高雄激素-胰岛素抵抗流产的可能作用机制。

方法

将动情周期规律且处于动情前期的SPF级雌性SD大鼠30只与SPF级雄性SD大鼠15只，于每日18：00按2∶1比例合笼，次日8：00雌鼠阴道涂片镜下观察到大量精子且见阴道栓视为妊娠第0.5天，共获得30只孕鼠。在妊娠第0.5天将孕鼠随机分为正常组、模型组、寿胎丸加味方组，每组10只。自妊娠第0.5天至第13.5天，寿胎丸加味方组予寿胎丸加味方药液26.6 g/（kg·d）灌胃，每天2次，连续14天；正常组和模型组同时予等体积生理盐水灌胃。除正常组外，其余两组孕鼠自妊娠第7.5天至第13.5天联合应用双氢睾酮和胰岛素腹腔注射，建立PCOS高雄-胰岛素抵抗流产大鼠模型。所有孕鼠于妊娠第0.5、3.5、6.5、9.5、12.5、14.5天测定体质量；于妊娠第14.5天取材，观察胚胎情况，计算胚胎丢失率、平均着床数及平均活胎数；透射电镜观察子宫蜕膜超微结构变化；Western Blot法检测子宫蜕膜组织中蛋白激酶R样内质网激酶（PERK）、真核翻译起始因子2α（eIF2α）蛋白水平；qRT-PCR法检测子宫蜕膜组织中内质网应激相关因子

Perk

、

Eif2α

、线粒体融合蛋白2（

Mfn2

）、葡萄糖调节蛋白78（

Grp78

）和蜕膜化相关因子Wnt家族成员4蛋白（

Wnt4

）、含FXYD域离子运输调控因子2（

Fxyd2

）、丝氨酸蛋白酶抑制剂家族G成员1（

Serping1

）、分泌型磷蛋白1（

Spp1

）、谷胱甘肽过氧化物酶3（

Gpx3

）、金属硫蛋白1G（

Mt1g

）mRNA表达情况。

结果

与正常组比较，模型组孕鼠在妊娠第9.5、12.5、14.5天体质量减少，

胚胎丢失率升高，平均着床数及平均活胎数降低，子宫蜕膜组织中PERK、eIF2α蛋白及mRNA表达升高，

Grp78

、

Fxyd2

、

Spp1

mRNA表达升高，

Mfn2

、

Wnt4

、

Serping1

、

Gpx3

、

Mt1g

mRNA表达降低（

＜0.05或

＜0.01）；子宫蜕膜超微结构显示细胞损伤明显，线粒体明显肿胀、膜局部隆起，内质网数量较多且明显扩张、脱颗粒。与模型组比较，寿胎丸加味方组孕鼠在妊娠第9.5、12.5、14.5天体质量增加，胚胎丢失率降低，平均活胎数升高，子宫蜕膜组织中PERK、eIF2α蛋白及mRNA表达降低，

Grp78、Fxyd2

、

Spp1

mRNA表达降低，

Mfn2

、

Wnt4

、

Serping1

、

Gpx3

mRNA表达升高（

＜0.05或

＜0.01）；子宫蜕膜细胞轻度损伤，线粒体数量较多、轻度固缩、膜完整，内质网数量减少、扩张、局部脱颗粒。

结论

寿胎丸加味方可能通过抑制PERK/eIF2α信号通路而改善子宫内膜内质网应激和蜕膜化受损，从而降低PCOS高雄激素-胰岛素抵抗流产模型大鼠的胚胎丢失率，防止流产发生。

Abstract

Objective

To explore the possible mechanism of the modified

Shoutai Pill

（寿胎丸） for polycystic ovary syndrome （PCOS） complicated by hyperandrogenism and insulin resistance-induced fetal loss.

Methods

Thirty SPF-grade female SD rats with regular estrous cycles and in the proestrus phase were caged with 15 SPF-grade male SD rats at a ratio of 2∶1 every day at 18：00. On the next day at 8：00， female rats were considered to be on day 0.5 of pregnancy when a large number of sperm and vaginal plugs were observed under a microscope in vaginal smears. A total of 30 pregnant rats were obtained. On day 0.5 of pregnancy， the pregnant rats were randomly divided into normal group， model group， and the modified

Shoutai Pill

group， with 10 rats in each group. From day 0.5 to day 13.5 of pregnancy， the

Shoutai Pill

group was given modified

Shoutai Pill

solution at a dose of 26.6 g/（kg·d） by gavage， twice a day， for 14 consecutive days. Meanwhile， the normal group and the model group were given an equal volume of normal saline by gavage. Except f

or the normal group， the pregnant rats were intraperitoneally injected with dihydrotestosterone and insulin from day 7.5 to day 13.5 of pregnancy to establish a PCOS rat model with hyperandrogenism and insulin resistance-induced fetal loss. All pregnant rats were weighed on days 0.5， 3.5， 6.5， 9.5， 12.5， and 14.5 of pregnancy； samples were collected on day 14.5 of pregnancy to observe the embryo status， and the embryo loss rate， average number of implantations， and average number of live fetuses were calculated； transmission electron microscopy was used to observe the ultrastructural changes of uterine decidua； Western Blot was performed to detect the protein levels of protein kinase R-like endoplasmic reticulum kinase （PERK） and eukaryotic translation initiation factor 2α （eIF2α） in uterine decidual tissues； qRT-PCR was used to detect the mRNA expression levels of endoplasmic reticulum stress-related factors （

Perk

，

Eif2α

， mitofusin 2 ［

Mfn2

］， glucose-regulated protein 78 ［

Grp78

］） and decidualization-related factors Wnt family member 4 ［

Wnt4

］， FXYD domain-containing ion transport regulator 2 ［

Fxyd2

］， serpin family G member 1 ［

Serping1

］， secreted phosphoprotein 1 ［

Spp1

］， glutathione peroxidase 3 ［

Gpx3

］， metallothionein 1G ［

Mt1g

］） in uterine decidual tissues.

Results

Compared with the normal group， the pregnant rats in the model group showed reduced body weight on days 9.5， 12.5， and 14.5 of pregnancy， an increased embryo loss rate， and decreased average number of implantations and average number of live fetuses， increased PERK and eIF2α protein and mRNA expressions in uterine decidual tissues， increased mRNA expressions of

Grp78

，

Fxyd2

， and

Spp1

， and reduced mRNA expressions of

Mfn2

，

Wnt4

，

Serping1

，

Gpx3

， and

Mt1g

（

＜0.05 or

＜0.01）； the ultrastructure of the uterine decidua showed obvious cellular damage， significant swelling of mitochondria， local bulging of membranes， as well as a relatively large number of endoplasmic reticula with obvious dilation and degranulation. Compared with the model group， the pregnant rats in

Shoutai Pill

group had increased body weight on days 9.5， 12.5， and 14.5 of pregnancy， a decreased embryo loss rate and an increased average number of live fetuses； decreased protein and mRNA expressions of PERK and eIF2α in uterine decidual tissues， reduced mRNA expressions of

Grp78

，

Fxyd2

， and

Spp1

， and elevated mRNA expressions of

Mfn2

，

Wnt4

，

Serping1

， and

Gpx3

（

＜0.05 or

＜0.01）； the uterine decidual cells showed mild damage， with a relatively large number of mitochondria， slightly pyknotic with intact membranes， but the number of endoplasmic reticula was reduced， with dilation and local degranulation.

Conclusion

The modified

Shoutai Pill

may improve endometrial endoplasmic reticulum stress and impaired decidualization by inhibiting the PERK/eIF2α signaling pathway， thereby reducing the embryo loss rate and preventing abortion in rats with PCOS complicated by hyperandrogenism and insulin resistance-induced fetal loss.

关键词

Keywords

references

BAHRI KHOMAMI M ， JOHAM AE ， BOYLE JA ， et al . Increased maternal pregnancy complications in polycystic ovary syndrome appear to be independent of obesity：a systematic review， meta-analysis， and meta-regression ［J］. Obes Rev ， 2019 ， 20 （ 5 ）： 659 - 674 .

韩晗，张跃辉，韩亚鹏，等 . 从铁死亡角度探讨寿胎丸加味方对PCOS早期先兆流产患者的疗效机制［J］. 中医药学报， 2023 ， 51 （ 10 ）： 67 - 71 .

郭婷婷，蒋蒙，杨怀影，等 . 寿胎丸加味方对多囊卵巢综合征高雄激素-胰岛素抵抗流产模型大鼠炎症反应和子宫内膜容受性相关因子表达的影响［J］. 中医杂志， 2025 ， 66 （ 3 ）： 275 - 282 .

ALEXANDRE-SANTOS B ， MARTINS FFTR ， DA SILVA GONÇALVES L ， et al . Potential role of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome ［J］. Horm Mol Biol Clin Investig ， 2022 ， 44 （ 1 ）： 105 - 112 .

KARAGUL MI ， YILDIRIM A ， DEMIRAY ASOGLU Z ， et al . Endoplasmic reticulum stress in myometrial smooth muscle cells and spontaneous contraction changes in the uterus of dehydroepiandrosterone-induced polycystic ovary syndrome rats ［J］. Cell Biochem Biophys ， 2025 ， 83 （ 1 ）： 893 - 904 .

HU M ， ZHANG Y ， GUO X ， et al . Hyperandrogenism and insulin resistance induce gravid uterine defects in association with mitochondrial dysfunction and aberrant reactive oxygen species production ［J］. Am J Physiol Endocrinol Metab ， 2019 ， 316 （ 5 ）： E794 - E809 .

ZHANG Y ， HU M ， YANG F ， et al . Increased uterine androgen receptor protein abundance results in implantation and mitochondrial defects in pregnant rats with hyperandrogenism and insulin resistance ［J］. J Mol Med （Berl）， 2021 ， 99 （ 10 ）： 1427 - 1446 .

GAO HJ ， ZHU YM ， HE WH ， et al . Endoplasmic reticulum stress induced by oxidative stress in decidual cells： a possible mechanism of early pregnancy loss ［J］. Mol Biol Rep ， 2012 ， 39 （ 9 ）： 9179 - 9186 .

MAHDI AA ， RIZVI SH ， PARVEEN A . Role of endoplasmic reticulum stress and unfolded protein responses in health and diseases ［J］. Indian J Clin Biochem ， 2016 ， 31 （ 2 ）： 127 - 137 .

ZHANG Y ， ZHAO W ， XU H ， et al . Hyperandrogenism and insulin resistance-induced fetal loss： evidence for placental mitochondrial abnormalities and elevated reactive oxygen species production in pregnant rats that mimic the clinical features of polycystic ovary syndrome ［J］. J Physiol ， 2019 ， 597 （ 15 ）： 3927 - 3950 .

魏伟，吴希美，李元健 . 药理实验方法学［M］. 北京：人民卫生出版社， 2010 ： 1698 .

马珺卓，靳梓琪，王天一，等 . 寿胎丸治疗复发性流产研究进展［J］. 河北中医， 2023 ， 45 （ 6 ）： 1038 - 1043 .

谭福红，李楠，张辉，等 . 寿胎丸对GnRHa控制性超促排卵着床期小鼠子宫内膜形态及妊娠结局的影响［J］. 实用妇科内分泌杂志（电子版）， 2019 ， 6 （ 6 ）： 64 - 65，73 .

VILLALOBOS-LABRA R ， SUBIABRE M ， TOLEDO F ， et al . Endoplasmic reticulum stress and development of insulin resistance in adipose， skeletal， liver， and foetoplacental tissue in diabesity ［J］. Mol Aspects Med ， 2019 ， 66 ： 49 - 61 . doi： 10.1016/j.mam.2018.11.001 http://dx.doi.org/10.1016/j.mam.2018.11.001 .

KYATHANAHALLI C ， ORGAN K ， MORECI RS ， et al . Uterine endoplasmic reticulum stress-unfolded protein response regulation of gestational length is caspase-3 and -7-dependent ［J ］. Proc Natl Acad Sci U S A ， 2015 ， 11 （ 45 ）： 14090 - 14095 .

SURESH A ， SUBEDI K ， KYATHANAHALLI C ， et al . Uterine endoplasmic reticulum stress and its unfolded protein response may regulate caspase 3 activation in the pregnant mouse uterus ［J］. PLoS One ， 2013 ， 8 （ 9 ）： e75152 .

SOCZEWSKI E ， GRASSO E ， GALLINO L ， et al . Immunoregulation of the decidualization program： focus on the endoplasmic reticulum stress ［J］. Reproduction ， 2020 ， 159 （ 4 ）： R203 - R211 .

BINET F ， SAPIEHA P . ER stress and angiogenesis ［J］. Cell Metab ， 2015 ， 22 （ 4 ）： 560 - 575 .

BRAAKMAN I ， BULLEID NJ . Protein folding and modification in the mammalian endoplasmic reticulum ［J］. Annu Rev Biochem ， 2011 ， 80 ： 71 - 99 . doi： 10.1146/annurev-biochem-062209-093836 http://dx.doi.org/10.1146/annurev-biochem-062209-093836 .

ALMANZA A ， CARLESSO A ， CHINTHA C ， et al . Endoplasmic reticulum stress signalling：from basic mechanisms to clinical applications ［J］. FEBS J ， 2019 ， 286 （ 2 ）： 241 - 278 .

SCHRÖDER M ， KAUFMAN RJ . Divergent roles of IRE1α and PERK in the unfolded protein response ［J］. Curr Mol Med ， 2006 ， 6 （ 1 ）： 5 - 36 .

ZHU G ， LEE AS . Role of the unfolded protein response， GRP78 and GRP94 in organ homeostasis ［J］. J Cell Physiol ， 2015 ， 230 （ 7 ）： 1413 - 1420 .

CAO Y ， CHEN Z ， HU J ， et al . Mfn2 regulates high glucose-induced MAMs dysfunction and apoptosis in podocytes via PERK pathway ［J］. Front Cell Dev Biol ， 2021 ， 9 ： 769213 . doi： 10.3389/fcell.2021.769213 http://dx.doi.org/10.3389/fcell.2021.769213 .

PITZER LM ， MORONEY MR ， NOKOFF NJ ， et al . WNT4 balances development vs disease in gynecologic tissues and women's health ［J］. Endocrinology ， 2021 ， 162 （ 7 ）： bqab093 .

PELLEGRINO M ， MAIORINO R ， SCHONAUER S . WNT4 signaling in female gonadal development ［J］. Endocr Metab Immune Disord Drug Targets ， 2010 ， 10 （ 2 ）： 168 - 174 .

FLOYD RV ， WRAY S ， QUENBY S ， et al . Expression and distribution of Na， K-ATPase isoforms in the human uterus ［J］. Reprod Sci ， 2010 ， 17 （ 4 ）： 366 - 376 .

GURUNG S ， GREENING DW ， RAI A ， et al . The proteomes of endometrial stromal cell-derived extracellular vesicles following a decidualizing stimulus define the cells' potential for decidualization success ［J］. Mol Hum Reprod ， 2021 ， 27 （ 10 ）： gaab057 .

GIBSON DA ， SIMITSIDELLIS I ， COUSINS FL ， et al . Intracrine androgens enhance decidualization and modulate expression of human endometrial receptivity genes ［J］. Sci Rep ， 2016 ， 6 ： 19970 . doi： 10.1038/srep19970 http://dx.doi.org/10.1038/srep19970 .

YAO S ， WEI W ， CAO R ， et al . Resveratrol alleviates zea-induced decidualization disturbance in human endometrial stromal cells ［J］. Ecotoxicol Environ Saf ， 2021 ， 207 ： 111511 . doi： 10.1016/j.ecoenv.2020.111511 http://dx.doi.org/10.1016/j.ecoenv.2020.111511 .

HU S ， YAO G ， WANG Y ， et al . Transcriptomic changes during the pre-receptive to receptive transition in human endometrium detected by RNA-Seq ［J］. J Clin Endocrinol Metab ， 2014 ， 99 （ 12 ）： E2744 - E2753 .

查看原文

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effect of Modified Shoutai Pill （寿胎丸加味方） on Inflammatory Reaction and Expression of Endometrial Receptivity-Related Factors in A Rat Model of Polycystic Ovary Syndrome and Miscarriage with High Testosterone-Insulin Resistance

Experience of XU Xin in Treating Polycystic Ovary Syndrome with Insulin Resistance Based on "Boost Kidney to Dispel the Turbid" Method

Effect of Jiawei Banxia Xiexin Decoction （加味半夏泻心汤） on Gut Microbiota and Inflammatory Factors in Polycystic Ovarian Syndrome with Insulin Resistance Model Rats

Clinical Observation on Qiangshen Tablets Combined With Longlu Capsules for 73 Cases of Polycystic Ovary Syndrome With Insulin Resistance

Differentiation and Treatment of Abnormal Uterine Bleeding Caused by Polycystic Ovary Syndrome Based on "Yangming （阳明） Turbid Heat" Theory

Related Author

YANG Huaiying

JI Xiang

ZHANG Yuehui

LIANG Jingqiao

JI Chengyu

LI Bo

许昕

ZHAO Hongyu

Related Institution

First Affiliated Hospital，Heilongjiang University of Chinese Medicine

Beijing Hospital of Traditional Chinese Medicine，Capital Medical University

Beijing Haidian Hospital

Beijing Institute of Traditional Chinese Medicine

Guang 'anmen Hospital，China Academy of Chinese Medical Sciences

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

Effects of Modified Shoutai Pill （寿胎丸） on Endoplasmic Reticulum Stress and Decidualization in the Endometrium for Hyperandrogenism and Insulin Resistance-Induced Fetal Loss of Rats with Polycystic Ovary Syndrome

DOI：10.13288/j.11-2166/r.2025.17.011

摘要

Abstract

关键词

Keywords

references