生殖医学杂志2025，Vol.34Issue(6)：817-825,9.DOI:10.3969/j.issn.1004-3845.2025.06.013
人脐带间充质干细胞外泌体对POI小鼠模型的治疗效果及治疗时间窗的探讨
Investigation on the therapeutic effects and time window of human umbilical cord mesenchymal stem cell exosomes on model mice with premature ovarian insufficiency
摘要
Abstract
Objective:To investigate the therapeutic effect and timing of human umbilical cord mesenchymal stem cell exosomes(HUMSCs-EXOs)on model mice with premature ovarian insufficiency(POI). Methods:A mouse model of POI was established by intraperitoneal injection of cyclophosphamide(CTX,120 mg/kg).Sixty female C57B6 mice with normal estrous cycle were randomly divided into model group,treatment group(injection of 2 μg/g HUMSCs-EXOs once a day)[including prevention group(before modeling),early treatment group(day 1 to 7 after modeling),middle treatment group(day 8 to 14 after modeling),late treatment group(day 15 to 21 after modeling)]and control group,with 10 mice in each group.On the 28th day after the successful modeling,the mice were anesthetized,blood was taken from the eyeballs,and the mice were killed to take bilateral ovaries.Serum reproductive hormone levels were detected by enzyme-linked immunosorbent assay(ELISA),serum antioxidant index levels were detected by microplate method,ovarian structural and morphological changes were observed by hematoxylin and eosin(HE)staining,and SIRT1 protein expression level was detected by immunohistochemistry.Four mice in each group were randomly selected and kept in a cage for 21 days with male mice at a ratio of 2∶1,and the number of offspring was recorded. Results:The POI group mice showed successful modeling compared to the control group.Compared with the POI group,the mice in the treatment group were generally better,with more weight gain,increased hormone levels of anti-Müllerian hormone(AM H),serum estradiol(E2),and LH,decreased hormone levels of FSH,increased antioxidant stress factors in terms of glutathione peroxidase(GSHPx)and superoxide dismutase(SOD),increased ovarian index,increased number of normal ovarian follicles,decreased number of atretic follicles,and increased expression level of SIRT 1 protein in the ovary,all showing statistical significance(P＜0.05).The comparison between the four treatment groups showed that the mice in the early and middle treatment groups were significantly better than those of the late treatment group and the prevention group in terms of general condition,weight gain,sex hormone level,oxidative stress level,ovarian index,the amount of normal ovarian follicles and SIRT1 protein expression level(P＜0.05). Conclusions:HUMSCs-EXOs can improve the ovarian function of POI mice,which may be related to oxidative stress,and early treatment with HUMSCs-EXOs has a better effect.关键词
早发性卵巢功能不全/人脐带间充质干细胞外泌体/氧化应激/SIRT1/治疗时间窗Key words
Premature ovarian insufficiency/HUMSCs-EXOs/Oxidative stress/SIRT1/Therapeutic time window分类
临床医学引用本文复制引用
刘利贞,刘萍,周超,尚丹丹,张英姿..人脐带间充质干细胞外泌体对POI小鼠模型的治疗效果及治疗时间窗的探讨[J].生殖医学杂志,2025,34(6):817-825,9.基金项目
海南省自然科学基金高层次人才项目(821RC732) （821RC732）
儋州市科技和工业信息发展局项目(儋科工信{2024｝79号) （儋科工信{2024｝79号）
山东省医药卫生科技项目(202405010551) （202405010551）
山东省中医药科技项目(2020M085) （2020M085）
滨州医学院"临床+X"项目(BY2021LCX26) （BY2021LCX26）
