Mechanism of placental polypeptide in improving ovarian function and oxidative stress in rats with premature ovarian failure

JIN Juan; XIAO Li; PU Qian; ZHANG Hua; YU Lei

doi:10.6039/j.issn.1001-0408.2024.21.06

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Mechanism of placental polypeptide in improving ovarian function and oxidative stress in rats with premature ovarian failure

更新时间：2024-11-08

- Mechanism of placental polypeptide in improving ovarian function and oxidative stress in rats with premature ovarian failure
- ZHONGGUO YAOFANG Vol. 35, Issue 21, Pages: 2609-2615(2024)
- 作者机构：
  
  1.贵州医科大学临床医学院，贵阳　550004
  2.黔南州人民医院产科，贵州都匀　558099
  3.贵阳市妇幼保健院中心实验室，贵阳　550004
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.21.06
  CLC： R965;R711.75
- Published：15 November 2024，
  
  Received：16 May 2024，
  
  Revised：18 September 2024，
- 稿件说明：
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金娟,肖丽,蒲茜等.胎盘多肽改善卵巢早衰大鼠卵巢功能及氧化应激的作用机制 ^Δ[J].中国药房,2024,35(21):2609-2615.

JIN Juan,XIAO Li,PU Qian,et al.Mechanism of placental polypeptide in improving ovarian function and oxidative stress in rats with premature ovarian failure[J].ZHONGGUO YAOFANG,2024,35(21):2609-2615.
金娟,肖丽,蒲茜等.胎盘多肽改善卵巢早衰大鼠卵巢功能及氧化应激的作用机制 ^Δ[J].中国药房,2024,35(21):2609-2615. DOI： 10.6039/j.issn.1001-0408.2024.21.06.

JIN Juan,XIAO Li,PU Qian,et al.Mechanism of placental polypeptide in improving ovarian function and oxidative stress in rats with premature ovarian failure[J].ZHONGGUO YAOFANG,2024,35(21):2609-2615. DOI： 10.6039/j.issn.1001-0408.2024.21.06.

摘要

目的

探究胎盘多肽调控Runt相关转录因子3（RUNX3）/Notch信号通路对环磷酰胺致卵巢早衰（POF）大鼠卵巢功能及氧化应激的影响。

方法

通过腹腔注射环磷酰胺构建POF大鼠模型。将造模成功的60只POF大鼠随机分为模型组、胎盘多肽低（1 mg/kg）、高（2 mg/kg）剂量组和胎盘多肽+空载质粒组（2 mg/kg胎盘多肽+1 μg空载质粒）以及胎盘多肽+RU

NX3沉默组[2 mg/kg胎盘多肽+1 μg RUNX3小干扰RNA质粒

]

，每组12只；另取12只健康大鼠作为对照组。以相应方法干预各组大鼠4周。末次给药后，测定大鼠血清中性激素[雌二醇（E

）、抗米勒管激素（AMH）、卵泡刺激素（FSH）

]

水平和卵巢组织中氧化应激指标[丙二醛（MDA）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、活性氧（ROS）

]

水平；检测大鼠卵巢组织病理和卵巢颗粒细胞凋亡情况；检测大鼠卵巢组织中凋亡相关蛋白[胱天蛋白酶3（caspase-3）、活化的caspase-3（cleaved-caspase-3）、B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（Bax）

]

与RUNX3/Notch信号通路相关蛋白的表达。

结果

与模型组比较，胎盘多肽低、高剂量组大鼠卵巢正常卵泡数量增加，闭锁卵泡数量显著减少，血清中E

、AMH水平和卵巢组织中SOD、CAT水平以及Bcl-2、RUNX3、Notch1蛋白表达水平均显著升高，血清中FSH水平、卵巢颗粒细胞凋亡率和卵巢组织中MDA、ROS水平以及cleaved-caspase-3、caspase-3、Bax蛋白表达水平均显著降低（

＜0.05）；且高剂量组的变化更明显（

＜0.05）。与胎盘多肽高剂量组和胎盘多肽+空载质粒组比较，胎盘多肽+RUNX3沉默组卵巢正常卵泡数量减少，上述指标水平显著逆转（

＜0.05）。

结论

胎盘多肽可能通过上调RUNX3/Notch信号通路，改善POF大鼠性激素分泌、氧化应激、卵巢颗粒细胞凋亡和卵巢功能，从而减轻其POF症状。

Abstract

OBJECTIVE

To explore the impact of placental polypeptide on the Runt-related transcription factor 3 （RUNX3）/Notch signaling pathway in rats with cyclophosphamide-induced premature ovarian failure （POF）， and its effects on ovarian function and oxidative stress.

METHODS

A POF rat model was induced by intraperitoneal injection of cyclophosphamide. Sixty POF rats of the model were randomly assigned to model group， low-dose （1 mg/kg） and high-dose （2 mg/kg） placental polypeptide groups， placental polypeptide plus empty vector group [placental polypeptide （2 mg/kg）， empty vector （1 μg）

]

， and placental polypeptide plus RUNX3 silencing group [placental polypeptide （2 mg/kg）， RUNX3 small interfering RNA （1 μg）

]

， with 12 rats in each group. Additionally， 12 healthy rats were selected as a control group. The intervention lasted for 4 weeks for all groups. After the final administration， the levels of sex hormones [estradiol （E

）， anti-Müllerian hormone （AMH）， follicle-stimulating hormone （FSH）

]

in rat serum and oxidative stress indicators [malondialdehyde （MDA）， superoxide dismutase （SOD）， ca

talase （CAT）， reactive oxygen species （ROS）

]

in ovarian tissue were measured. The pathology of rat ovarian tissue and apoptosis of ovarian granulosa cells were examined； the expression of apoptosis-related proteins [caspase-3， cleaved-caspase-3， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）

]

and RUNX3/Notch signaling pathway-related proteins in rat ovarian tissue were detected.

RESULTS

Compared with the model group， the low and high doses of placental polypeptide groups showed an increase in the number of normal follicles and a marked decrease in the number of atretic follicles， with significant increases in the serum levels of E

and AMH， the ovarian tissue levels of SOD and CAT， as well as the expression levels of Bcl-2， RUNX3 and Notch1 proteins， and significant decreases in the serum FSH levels， the ovarian granulosa cell apoptosis rate， and the ovarian tissue levels of MDA and ROS， as well as the expression levels of cleaved-caspase-3， caspase-3 and Bax proteins （

＜0.05）； the changes in the high-dose group were significantly more pronounced （

＜0.05）. Compared with the high-dose placental polypeptide group and the placental polypeptide plus empty vector group， the placental polypeptide plus RUNX3 silencing group showed a decrease in the number of normal follicles and a significant reversal of the above indicators （

＜0.05）.

CONCLUSIONS

Placental polypeptide may alleviate the symptoms of rats with POF by upregulating the RUNX3/Notch signaling pathway， improving sex hormone secretion， oxidative stress， ovarian granulosa cell apoptosis and ovarian function.

关键词

胎盘多肽卵巢早衰Runt相关转录因子3Notch卵巢功能氧化应激

Keywords

premature ovarian failureRunt-related transcription factor 3Notchovarian functionoxidative stress

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