Effect of <italic style="font-style: italic">Jianwei Shoutai Pill</italic> （减味寿胎丸） on Lipid Peroxidation and Ferroptosis Protein Expression in Decidua of Abortion Rats

Yuling LAI; Yingxuan ZHANG; Lihua ZENG; Gaopi DENG; Songping LUO; Jie GAO

doi:10.13288/j.11-2166/r.2021.21.013

您当前的位置：

首页 >

文章列表页 >

Effect of Jianwei Shoutai Pill （减味寿胎丸） on Lipid Peroxidation and Ferroptosis Protein Expression in Decidua of Abortion Rats

更新时间：2021-11-02

- Effect of Jianwei Shoutai Pill （减味寿胎丸） on Lipid Peroxidation and Ferroptosis Protein Expression in Decidua of Abortion Rats
- Journal of Traditional Chinese Medicine Vol. 62, Issue 21, Pages: 1917-1922(2021)
- 作者机构：
  
  1.广州中医药大学第一临床医学院，广东省广州市白云区机场路12号，510545
  2.广州中医药大学第一附属医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2021.21.013
  CLC：
- Received：22 April 2021，
  
  Revised：2021-07-21，
  
  Published：02 November 2021
- 稿件说明：
移动端阅览
赖裕玲,张莹轩,曾丽华等.减味寿胎丸对流产模型大鼠子宫蜕膜脂质过氧化及铁死亡蛋白表达的影响[J].中医杂志,2021,62(21):1917-1922.

LAI Yuling,ZHANG Yingxuan,ZENG Lihua,et al.Effect of Jianwei Shoutai Pill （减味寿胎丸） on Lipid Peroxidation and Ferroptosis Protein Expression in Decidua of Abortion Rats[J].Journal of Traditional Chinese Medicine,2021,62(21):1917-1922.
赖裕玲,张莹轩,曾丽华等.减味寿胎丸对流产模型大鼠子宫蜕膜脂质过氧化及铁死亡蛋白表达的影响[J].中医杂志,2021,62(21):1917-1922. DOI： 10.13288/j.11-2166/r.2021.21.013.

LAI Yuling,ZHANG Yingxuan,ZENG Lihua,et al.Effect of Jianwei Shoutai Pill （减味寿胎丸） on Lipid Peroxidation and Ferroptosis Protein Expression in Decidua of Abortion Rats[J].Journal of Traditional Chinese Medicine,2021,62(21):1917-1922. DOI： 10.13288/j.11-2166/r.2021.21.013.

摘要

目的

探讨减味寿胎丸治疗流产的潜在分子机制。

方法

SD雌性及雄性大鼠各48只，按雌、雄1∶1合笼持续配种2周，以观察到阴道栓作为妊娠第0天，共获得妊娠大鼠40只，随机分为正常组、模型组、地屈孕酮组、减味寿胎丸组，每组10只。自妊娠第0天开始，正常组和模型组雌鼠予10 ml/（kg·d）纯水灌胃，减味寿胎丸组予减味寿胎丸药液1.8 g/（kg·d）灌胃，地屈孕酮组予地屈孕酮片5.4 mg/（kg·d）灌胃，每日1次，连续13天。在妊娠第13天上午，模型组、地屈孕酮和减味寿胎丸组予浓度为1.2 mg/ml米非司酮药液10 ml/kg灌胃建立流产大鼠模型。妊娠第14天取材，HE染色观察各组大鼠子宫蜕膜组织的病理形态改变，检测蜕膜组织脂质过氧化相关指标［还原型谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GPX）、丙二醛（MDA）］水平及总铁离子［Fe

（Ⅱ+Ⅲ）

］含量，普鲁士蓝（Perls）染色检测大鼠蜕膜组织铁离子分布，免疫组化及Western Blot法检测蜕膜组织铁死亡关键蛋白［谷胱甘肽过氧化物酶4（GPX4）、溶质载体家族7成员11（SLC7A11）、转铁蛋白受体1（TFR1）］蛋白分布及相对表达量。

结果

HE染色结果显示，正常组大鼠蜕膜组织血管丰富，蜕膜细胞排列紧密；模型组大鼠蜕膜组织血管分布少，胞浆水肿，部分细胞核消失；地屈孕酮组及减味寿胎丸组大鼠蜕膜组织病理较模型组明显改善。模型组大鼠较正常组蜕膜组织中GSH、GPX水平及GPX4、SLC7A11蛋白表达降低，Fe

（Ⅱ+Ⅲ）

含量、MDA水平及TFR1蛋白表达升高（

＜0.05或

＜0.01）。与模型组比较，减味寿胎丸组大鼠蜕膜组织中GSH、GPX水平及GPX4、SLC7A11蛋白表达升高，MDA水平、Fe

（Ⅱ+Ⅲ）

含量、TFR1蛋白表达降低（

＜0.05或

＜0.01）；地屈孕酮组GPX水平升高，Fe

（Ⅱ+Ⅲ）

含量降低（

＜0.01）。地屈孕酮组与减味寿胎丸组各指标差异均无统计学意义（

P＞

0.05）。

结论

减味寿胎丸可减轻流产大鼠脂质过氧化及过度铁累积，抑制子宫蜕膜组织铁死亡，从而防止流产的发生。

Abstract

Objective

To explore the underlying mechanism of

Jianwei Shoutai Pill

（减味寿胎丸， JSP） in treating abortion.

Methods

Forty-eight male rats were bred in cages with 48 female rats at the ratio of 1∶1 for two weeks； and day 0 of pregnancy was when the vaginal suppository was found. Forty rats with successful pregnancy were randomized into normal group， model group， dydrogesterone group and JSP group with ten rats in each group. From day 0 of pregnancy， rats in the normal group and model group were given 10 ml/（kg·d） pure water by gavage； the JSP group was administered with 1.8 g/（kg·d） JSP by gavage， and the dydrogesterone group was given 5.4 mg/（kg·d） didroxyprogesterone by gavage； all the administrations were given once daily for 13 days. The abortion rat model was established in the model group， dydrogesterone group and JSP group by gavage with 10 ml/kg mifepristone solution at a concentration of 1.2 mg/ml on day 13 of pregnancy， and decidual tissues were collected on day 14 of pregnancy. HE staining was used to observe the pathological changes of decidual tissue， and to detect the levels of lipid peroxidation-related indexes including reduced glutathione （GSH）， glutathione peroxidase （GPX）， malondialdehyde （MDA））， as well as the content of total iron （Fe

（Ⅱ+Ⅲ）

）. Prussian blue （Perls） staining was used to detect the distribution of iron ion in the decidua tissue， and the immunohistochemistry and Western Blot method were used to detect the protein distribution and relative expressions of glutathione peroxidase 4 （GPX4）， solute carrier family 7 member 11 （SLC7A11） and transferrin receptor 1 （TFR1） which could reflect ferroptosis.

Results

The HE staining results indicated that the decidual tissue of the rats in the normal group was rich in blood vessels， and the decidual cells were tightly arranged； the decidual tissue in the model group had less blood vessels， with cytoplasmic edema and partially missing nucleus； the dydrogesterone group and the JSP group had improved pathological results of decidual tissue than the model group. Compared to the normal group， the model group had significantly lower GSH and GPX levels， and GPX4 and SLC7A11 protein expression， as well as higher Fe

（Ⅱ+Ⅲ）

content， MDA level and TFR1 protein expression in decidual tissue （

＜0.05 or

＜0.01）. Compared to the model group， the JSP group significantly increased the GSH， GPX levels， GPX4 and SLC7A11 protein expression， and reduced the MDA level， Fe

（Ⅱ+Ⅲ）

content and TFR1 protein expression （

＜0.05 or

＜0.01）； the dydrogesterone group had higher GPX level and lower Fe

（II+III）

content （

＜0.01）. There were no significant differences between dydrogesterone group and JSP group in all indexes.

Conclusion

JSP may reduce lipid peroxidation and excessive iron accumulation to inhibit ferroptosis in the decidual tissue， thereby preventing abortion ultimately.

关键词

Keywords

references

LARSEN EC ， CHRISTIANSEN OB ， KOLTE AM ， et al . New insights into mechanisms behind miscarriage ［J］. BMC Med ， 2013 ， 11 ： 154 . doi： 10.1186/1741-7015-11-154 http://dx.doi.org/10.1186/1741-7015-11-154 .

BAI RX ， TANG ZY . Long non-coding RNA H19 regulates Bcl-2， Bax and phospholipid hydroperoxide glutathione peroxidase expression in spontaneous abortion ［J］. Exp Ther Med ， 2021 ， 21 （ 1 ）： 41 .

NG SW ， NORWITZ SG ， NORWITZ ER . The impact of iron overload and ferroptosis on reproductive disorders in humans： implications for preeclampsia ［J］. Int J Mol Sci ， 2019 ， 20 （ 13 ）： 3283 .

HAN D ， JIANG L ， GU X ， et al . SIRT3 deficiency is resistant to autophagy-dependent ferroptosis by inhibiting the AMPK/mTOR pathway and promoting GPX4 levels ［J］. J Cell Physiol ， 2020 ， 235 （ 11 ）： 8839 - 8851 .

DIXON SJ ， LEMBERG KM ， LAMPRECHT MR ， et al . Ferroptosis： an iron-dependent form of nonapoptotic cell death ［J］. Cell ， 2012 ， 149 （ 5 ）： 1060 - 1072 .

周月希，余庆英，罗颂平，等 . 减味寿胎丸对自然流产模型小鼠子宫蜕膜组织中FOXO3及PR蛋白表达的影响［J］. 中医杂志， 2021 ， 62 （ 4 ）： 335 - 340 .

郝晓丽，王冬盈，郜洁，等 . 寿胎丸减味方对肾虚自然流产模型小鼠IL-17的影响［J］. 世界中西医结合杂志， 2020 ， 15 （ 2 ）： 292 - 295 .

TELLERIA CM ， DEIS RP . Reproductive function in rats after mifepristone-induced termination of pregnancy ［J］. Contraception ， 1996 ， 53 （ 3 ）： 185 - 190 .

CAMILLERI C ， BEITER RM ， PUENTES L ， et al . Biological， behavioral and physiological consequences of drug-induced pregnancy termination at first-trimester human equivalent in an animal model ［J］. Front Neurosci ， 2019 ， 13 ： 544 . doi： 10.3389/fnins.2019.00544 http://dx.doi.org/10.3389/fnins.2019.00544 .

RAI R ， REGAN L . Recurrent miscarriage ［J］. Lancet ， 2006 ， 368 （ 9535 ）： 601 - 611 .

冯婷．减味寿胎丸补肾安胎有效部位对RU486 诱导滋养细胞损伤模型的影响［D］．广州：广州中医药大学， 2014 ．

BEHARIER O ， TYURIN VA ， GOFF JP ， et al . PLA2G6 guards placental trophoblasts against ferroptotic injury ［J］. Proc Natl Acad Sci U S A ， 2020 ， 117 （ 44 ）： 27319 - 27328 .

ZHANG Y ， HU M ， JIA W ， et al . Hyperandrogenism and insulin resistance modulate gravid uterine and placental ferroptosis in PCOS-like rats ［J］. J Endocrinol ， 2020 ， 246 （ 3 ）： 247 - 263 .

HCINI N ， JOLIVET A ， POMAR L ， et al . Cervical maturation using mifepristone in women with normal pregnancies at or beyond term ［J］. Eur J Obstet Gynecol Reprod Biol ， 2020 ， 248 ： 58 - 62 . doi： 10.1016/j.ejogrb. 2020. 03.020 http://dx.doi.org/10.1016/j.ejogrb.2020.03.020 .

STOCKWELL BR ， FRIEDMANN ANGELI JP ， BAYIR H ， et al . Ferroptosis： a regulated cell death nexus linking metabolism， redox biology， and disease ［J］. Cell ， 2017 ， 171 （ 2 ）： 273 - 285 .

FRIEDMANN AJ ， KRYSKO DV ， CONRAD M . Ferroptosis at the crossroads of cancer-acquired drug resistance and immune evasion ［J］. Nat Rev Cancer ， 2019 ， 19 （ 7 ）： 405 - 414 .

KOPPULA P ， ZHANG Y ， ZHUANG L ， et al . Amino acid transporter SLC7A11/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer ［J］. Cancer Commun （Lond）， 2018 ， 38 （ 1 ）： 12 .

BROWN R ， RICHARDSON KL ， KABIR TD ， et al . Altered iron metabolism and impact in cancer biology， metastasis， and immunology ［J］. Front Oncol ， 2020 ， 10 ： 476 . doi： 10.3389/fonc.2020.00476 http://dx.doi.org/10.3389/fonc.2020.00476 .

GRUBER CJ ， HUBER JC . The role of dydrogesterone in recurrent （habitual） abortion ［J］. J Steroid Biochem Mol Biol ， 2005 ， 97 （ 5 ）： 426 - 430 .

BUREAU I ， LAPORTE F ， FAVIER M ， et al . No antioxidant effect of combined HRT on LDL oxidizability and oxidative stress biomarkers in treated post-menopausal women ［J］. J Am Coll Nutr ， 2002 ， 21 （ 4 ）： 333 - 338 .

查看原文

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Discussion on the Role of Ferroptosis in Chronic Obstructive Pulmonary Disease from the Perspective of "Qi Deficiency with Retention and Stagnation"

Treatment of Lung Cancer Based on Ferroptosis：from the Theory of Yin-Yang Qi Transformation

Effects of Bushen Zhichan Formula （补肾止颤方） on Ferroptosis of Dopaminergic Neurons and Nrf2-Regulated SLC7A11/GSH/GPX4 Signaling Pathway in Parkinson's Disease Model Rats

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

Effect of Shipi Xiaoji Beverage（实脾消积饮）-containing Serum on Mitochondrial Dynamics Imbalance and Ferroptosis of Liver Cancer HepG2 Cells

Related Author

YANG Qinjun

LI Zegeng

TONG Jiabing

YANG Cheng

ZENG Dian

XIA Heyue

ZHU Hongyu

GAO Yuchen

Related Institution

Anhui Provincial Key Laboratory of Translational Research on Major Pulmonary Diseases Prevention and Treatment by Traditional Chinese Medicine

First Affiliated Hospital of Anhui University of Traditional Chinese Medicine

Anhui University of Traditional Chinese Medicine

Guang'anmen Hospital，China Academy of Chinese Medical Sciences

Beijing University of Chinese Medicine

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 Jianwei Shoutai Pill （减味寿胎丸） on Lipid Peroxidation and Ferroptosis Protein Expression in Decidua of Abortion Rats

DOI：10.13288/j.11-2166/r.2021.21.013

摘要

Abstract

关键词

Keywords

references