来源于脂肪间充质干细胞的外泌体促进宫腔粘连大鼠子宫内膜再生和生育能力恢复的机制研究  

The Mechanism of Exosomes Derived from Adipose-derived Mesenchymal Stem Cells Promoting Endometrial Regeneration and Fertility Recovery in Rats with Intrauterine Adhesions

作　　者：汪玲莉 林岚 韩春龙 吴小玲 贾晋 张莹 王小红 WANG Ling-li;LIN Lan;HAN Chun-long;WU Xiao-ling;JIA Jin;ZHANG Ying;WANG Xiao-hong(Fujian University of Traditional Chinese Medicine Affiliated People's Hospital(Fujian Provincial People's Hospital)Gynecology,Fuzhou,Fujian,350004,China)

机构地区：[1]福建中医药大学附属人民医院(福建省人民医院)妇科,福建福州1350004

出　　处：《现代生物医学进展》2024年第7期1221-1227,共7页Progress in Modern Biomedicine

基　　金：福建省卫健委科技计划项目(2020GGB037);福建省妇科微创与整合盆底临床研究中心项目(X202201)。

摘　　要：目的:本研究旨在鉴定来源于脂肪间充质干细胞的外泌体(ADSC-exo),并探索其在宫腔粘连(Intrauterine adhesion,IUA)大鼠模型中的治疗潜力。方法:从6-8周龄的雌性Sprague-Dawley大鼠获得腹股沟脂肪组织,并且分离ADSC。而流式细胞术分析用于鉴定ADSC的细胞表面标志物(CD90、CD105、CD34和CD45)的表达。与透射电子显微镜观察外泌体形态,蛋白质免疫印迹法分析外泌体表面标记蛋白(CD63和Alix)的表达。苏木精伊红染色和马松染色分别分析子宫组织的形态和纤维化情况。进行功能测试评估IUA大鼠的妊娠率、着床胚胎数和受孕时间。结果:ADSC-exo呈典型的杯状形态,Alix和CD63阳性表达,主要集中在109.5nm处。在IUA模型中,ADSC-exO能增强整合素β3、LIF和VEGF的表达,并且能促进子宫内膜再生和胶原重塑,及维持正常子宫结构。ADSC-exo可以改善再生子宫内膜容受性。结论:ADSC-exo能促进子宫内膜再生和生育力恢复。本研究的结果提示严重宫腔粘连和不孕症采用ADSC-exO子宫内局部给药治疗是一种潜在的有效方案。Objective:The purpose of this study was to identify exosomes derived from adipose-derived mesenchymal stem cells(ADSC-exo)and to explore its therapeutic potential in the rat model of intrauterine adhesion(IUA).Methods:Inguinal adipose tissue was obtained from 6-8-week-old female Sprague-Dawley rats and ADSC was isolated.Flow cytometry analysis was used to identify the expression of cell surface markers(CD90,CD105,CD34 and CD45)of ADSC.The morphology of exosomes was characterized by transmission electron microscopy,and the expression of exosome surface marker proteins(CD63 and Alix)was analyzed by Western blotting.Hematoxylin eosin staining and Masson staining were used to analyze the morphology and fibrosis of uterine tissue.Functional tests were performed to evaluate the pregnancy rate,number of implanted embryos and pregnancy time of IUA rats.Results:ADSC-exo was cup-shaped and expressed Alix and CD63 mainly at 109.5 nm.In IUA model,ADSC-exo enhanced integrinβ3,LIF and VEGF expression,promoted endometrial regeneration and collagen remodeling,and maintained normal uterine structure.ADSC-exo can improve the receptivity of regenerating endometrium.Conclusion:ADSC-exo promotes endometrial regeneration and fertility recovery.The results of this study suggest that ADSC-exo is a potentially effective treatment option for severe intrauterine adhesions and infertility by local intrauterine administration.

关 键 词：脂肪间充质干细胞 外泌体 宫腔粘连 子宫内膜再生 生育能力 

分 类 号：R-33[医药卫生] R711.3