经血来源子宫内膜干细胞外泌体恢复卵巢早衰大鼠卵巢功能的效果及机制研究

徐丽雅; 程丽; 程贤鹦; 吴燕琴; 刘敏杰; 颜光翰; 章婷; 许震宇

doi:10.16766/j.cnki.issn.1674-4152.004407

经血来源子宫内膜干细胞外泌体恢复卵巢早衰大鼠卵巢功能的效果及机制研究

doi: 10.16766/j.cnki.issn.1674-4152.004407

1.
浙江树人大学树兰国际医学院附属树兰(杭州)医院妇产科，浙江杭州 310022
2.
杭州市西溪医院妇产科，浙江杭州 310023
3.
浙江树人大学树兰国际医学院附属树兰(杭州)医院检验科
4.
浙江树人大学树兰国际医学院附属树兰(杭州)医院病理科
5.
浙江生创精准医疗科技有限公司，浙江杭州 310022

基金项目:

浙江省中医药科技计划项目 2023ZL591

杭州市卫生科技计划项目 20220020

杭州市拱墅区医药卫生科技计划项目 A202208

详细信息

通讯作者:
程贤鹦，E-mail：logancxy1982@163.com

中图分类号: R711.75 R332
计量
- 文章访问数: 14
- HTML全文浏览量: 9
- PDF下载量: 1
- 被引次数: 0
出版历程
- 收稿日期: 2025-02-10
- 网络出版日期: 2026-06-02

Effects and mechanism of exosomes derived from menstrual blood-derived stromal cells in restoring ovarian function in a rat model of premature ovarian failure

1.
Department of Obstetrics and Gynecology, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang 310022, China

摘要

摘要: 目的本研究探讨经血来源子宫内膜干细胞外泌体(MenSCs-Exos)对卵巢早衰(POF)大鼠卵巢功能的修复作用及其机制。方法 POF模型建成后采用随机数字表法分为移植治疗组和安慰剂组(各8只)，接受MenSCs-Exos和PBS尾静脉注射，设立空白对照组(8只)。观察大鼠一般情况、动情周期和体重变化，采用ELISA法检测黄体生成素(LH)、卵泡刺激素(FSH)、抗缪勒管激素(AMH)、雌二醇(E2)、B细胞淋巴瘤-2(Bcl-2)和Bcl-2相关X蛋白(Bax)浓度，HE染色并观察大鼠卵巢组织病理变化，计数各级卵泡数。结果干预后移植治疗组大鼠一般情况改善，动情周期恢复，干预第14天移植治疗组大鼠体重[(289.56±10.80)g]小于空白对照组[(313.38±8.94)g]，高于安慰剂组[(280.82±4.40)g，P＜0.05]。移植治疗组LH和FSH水平低于安慰剂组，高于空白对照组，AMH和E2水平则明显高于安慰剂组，低于空白对照组(P＜0.05)，移植治疗组大鼠卵巢病理形态得到改善，各级卵泡数量均低于空白对照组，高于安慰剂组(P＜0.05)。移植治疗组Bcl-2浓度低于空白对照组，高于安慰剂组，而Bax浓度则高于空白对照组，低于安慰剂组(P＜0.05)。结论 MenSCs-Exos移植可恢复CTX所致POF大鼠的卵巢功能，改善卵巢组织损伤，其机制可能与凋亡相关蛋白表达的调节有关。
- 经血来源子宫内膜干细胞 /
- 外泌体 /
- 卵巢早衰 /
- 卵巢功能
Abstract: Objective The purpose of this study was to explore the reparative effects and mechanisms of exosomes derived from menstrual blood-derived stromal cells (MenSCs-Exos) in restoring ovarian function of premature ovarian failure (POF) rats. Methods After the POF model was successfully established, it was divided into the transplantation treatment group and the placebo group (each 8 rats) using the random number table method. Both groups received tail vein injections of MenSCs-Exos and PBS. Control group (8 rats) was also set up. The physical conditions, body weight, and estrus cycle of the SD rats were monitored. Plasma was harvested to measure the levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), anti-Mullerian hormone (AMH), and estradiol (E2) by ELISA. The ovarian pathology and follicle counts were examined by HE. The protein concentration of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in ovarian tissue were examined by ELISA. Results Rats in the transplantation group restored physical condition and the motility cycle after treatment. On day 14 after intervention, the weight of rats in the transplantation group was lower [(289.56±10.80) g] than that of the control group [(313.38±8.94) g] and higher than that of the placebo group [(280.82±4.40) g, P < 0.05]. The levels of LH and FSH in the transplantation group were significantly lower than those in the placebo group and higher than those in the control group, while the levels of AMH and E2 were significantly higher than those in the placebo group and lower than those in the control group (P < 0.05). The pathological morphology of the ovaries in the transplantation group was improved, with follicle numbers at all developmental stages lower than those of the control group and higher than those of the placebo group (P < 0.05). In addition, the concentration of Bcl-2 protein was lower than that of the control group and higher than that of the placebo group, while the concentration of Bax protein was higher than that of the control group and lower than that of the placebo group (P < 0.05). Conclusion MenSCs-Exos transplantation effectively restores ovarian function and ameliorates ovarian damage, potentially through regulation of apoptosis-related protein expression.
- Premature ovarian failure /
- Menstrual blood-derived endometrial stem cells /
- Exosomes /
- Ovarian function

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图 1 实验期间大鼠动情周期、体重变化趋势及卵巢组织形态学变化

注：A为建模期间2组大鼠动情周期变化；B为建模期间2组大鼠体重变化；C为干预期间3组大鼠动情周期变化；D为干预期间3组大鼠体重变化；E为卵巢病理组织形态(HE染色，×100)，白色箭头示原始卵泡，红色箭头示初级卵泡，黄色箭头示次级卵泡，绿色箭头示窦状卵泡，黑色箭头示闭锁卵泡。

Figure 1. Estrous cycle, weight change trend and ovarian histomorphological changes of rats during the experimental period

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表 1 建模后2组大鼠体重及血清性激素比较(x±s)

Table 1. Comparison of body weight and serum sex hormones between the two groups after modeling (x±s)

组别	只数	第14天体重 (g)	LH (mIU/mL)	FSH (mIU/mL)	AMH (pg/mL)	E2 (pmol/L)
空白对照组	8	302.44±9.69	18.60±2.96	18.72±2.36	4 646.82±347.06	45.88±4.19
CTX组	16	267.94±12.63	53.92±3.72	39.42±3.48	2 075.34±252.96	14.19±0.98
t值		7.566	24.790	15.871	23.852	29.312
P值		< 0.001	< 0.001	< 0.001	< 0.001	< 0.001

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表 2 干预后3组大鼠体重及血清性激素比较(x±s)

Table 2. Comparison of body weight and serum sex hormones among the three groups after intervention (x±s)

组别	只数	第14天体重(g)	LH(mIU/mL)	FSH(mIU/mL)	AMH(pg/mL)	E2(pmol/L)
空白对照组	8	313.38±8.94	18.77±3.97	18.94±2.39	4 628.28±202.52	43.36±5.62
移植治疗组	8	289.56±10.80^a	37.04±3.81^a	28.28±2.24^a	3 728.38±315.32^a	29.96±3.68^a
安慰剂组	8	280.82±4.40^ab	53.88±3.54^ab	39.37±3.05^ab	2 251.86±441.78^ab	14.23±0.68^ab
F值		55.301	118.032	111.889	94.247	111.828
P值		< 0.001	< 0.001	< 0.001	< 0.001	< 0.001
注：与空白对照组比较，^aP < 0.05；与移植治疗组比较，^bP < 0.05。

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表 3 干预后3组大鼠卵巢各级卵泡数量比较(x±s, 个)

Table 3. Comparison of the number of ovarian follicles at all levels in the three groups after intervention (x±s, number)

组别	只数	原始卵泡	初级卵泡	次级卵泡	窦状卵泡
空白对照组	8	10.13±1.89	7.25±2.12	7.15±1.62	7.13±2.90
移植治疗组	8	6.63±1.69^a	5.13±1.13^a	4.13±1.89^a	3.38±2.07^a
安慰剂组	8	2.63±1.85^ab	1.25±1.04^ab	0.75±0.71^ab	1.13±0.83^ab
F值		34.477	32.478	29.651	16.486
P值		< 0.001	< 0.001	< 0.001	< 0.001
注：与空白对照组比较，^aP < 0.05；与移植治疗组比较，^bP < 0.05。

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表 4 3组大鼠卵巢组织Bcl-2和Bax蛋白浓度比较(x±s, ng/mL)

Table 4. Comparison of Bcl-2 and Bax protein concentrations in ovarian tissue of rats in three groups (x±s, ng/mL)

组别	只数	Bcl-2	Bax
空白对照组	8	151.52±9.44	7.95±0.42
移植治疗组	8	128.31±2.81^a	8.78±0.64^a
安慰剂组	8	97.53±3.33^ab	9.70±0.63^ab
F值		129.183	16.403
P值		< 0.001	< 0.001
注：与空白对照组比较，^aP < 0.05；与移植治疗组比较，^bP < 0.05。

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