中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (31): 8068-8076.doi: 10.12307/2026.883

• 脂肪干细胞 adipose-derived stem cells • 上一篇    下一篇

miR-122-5p转染人脂肪间充质干细胞外泌体治疗大鼠宫腔粘连

覃  颖1，2，陈继冰3，梁维萍3，经文瑶1，朱湘芸1，何君葵1，庞丽红1，李红丽3   

  1. 1广西医科大学第一附属医院产前诊断与遗传病诊断科，广西壮族自治区南宁市  530021；2贵港市人民医院产科，广西壮族自治区贵港市  537100；3广西中医药大学附属瑞康医院中西医结合转化医学中心，广西壮族自治区南宁市  530012
  • 收稿日期:2026-01-14 接受日期:2026-02-13 出版日期:2026-11-08 发布日期:2026-05-22
  • 通讯作者: 李红丽，博士，助理研究员，广西中医药大学附属瑞康医院中西医结合转化医学中心，广西壮族自治区南宁市 530012； 共同通讯作者：庞丽红，博士，主任医师，教授，广西医科大学第一附属医院产前诊断与遗传病诊断科，广西壮族自治区南宁市 530021
  • 作者简介:覃颖，女，1986年生，壮族，广西医科大学在读博士，副主任医师，主要从事妇产科学研究。
  • 基金资助:
    国家自然科学基金项目(82260306，81960281)，项目负责人：庞丽红；广西重点研发计划-临床干预方案构建(AB24010080)，项目负责人：庞丽红；广西中医药大学博士科研启动基金(2021BS032)，项目负责人：李红丽

miR-122-5p-transfected exosomes from human adipose-derived mesenchymal stem cells for treatment of intrauterine adhesions in rats

Qin Ying1, 2, Chen Jibing3, Liang Weiping3, Jing Wenyao1, Zhu Xiangyun1, He Junkui1, Pang Lihong1, Li Hongli3   

  1. 1Department of Prenatal Diagnosis and Genetic Diagnosis, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China; 2Department of Obstetrics, Guigang City People's Hospital, Guigang 537100, Guangxi Zhuang Autonomous Region, China; 3Center for Translational Medical Research in Integrative Chinese and Western Medicine, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530012, Guangxi Zhuang Autonomous Region, China
  • Received:2026-01-14 Accepted:2026-02-13 Online:2026-11-08 Published:2026-05-22
  • Contact: Li Hongli, PhD, Assistant researcher, Center for Translational Medical Research in Integrative Chinese and Western Medicine, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530012, Guangxi Zhuang Autonomous Region, China; Co-corresponding author: Pang Lihong, PhD, Chief physician, Professor, Department of Prenatal Diagnosis and Genetic Diagnosis, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
  • About author:Qin Ying, MD candidate, Associate chief physician, Department of Prenatal Diagnosis and Genetic Diagnosis, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China; Department of Obstetrics, Guigang City People's Hospital, Guigang 537100, Guangxi Zhuang Autonomous Region, China
  • Supported by:
    National Natural Science Foundation of China, No. 82260306, 81960281 (to PLH); Construction of Clinical Intervention Protocols Guangxi Key R & D Program, No. AB24010080 (to PLH); Doctoral Research Startup Fund of Guangxi University of Chinese Medicine, No. 2021BS032 (to LHL)

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摘要：

文题释义：

外泌体：是细胞外囊泡的一种，直径在30-150 nm之间，具有脂质双分子层结构，内含蛋白质、核酸(如mRNA、miRNA、DNA)、脂质等生物活性分子，参与细胞间通讯和多种生理病理过程。
宫腔粘连：又称 Asherman综合征，是指子宫内膜基底层受损后，子宫壁之间形成异常粘连带，导致宫腔部分或全部闭塞。

摘要
背景：miRNA作为重要的基因表达调控分子，在组织修复中发挥关键作用，而外泌体是很有前景的药物载体，为递送miRNA进行靶向治疗提供了新的策略。
目的：探讨过表达miR-122-5p的脂肪间充质干细胞外泌体对大鼠宫腔粘连的治疗效果。
方法：收集宫腔粘连患者和正常无宫腔粘连患者的子宫内膜组织，采用qPCR检测miR-122-5p的表达差异。通过慢病毒载体转染方法将miR-122-5p转染至人脂肪间充质干细胞中，采用3D FloTrix viva Exo外泌体收获系统提取外泌体。将36只雌性SD大鼠随机分为正常组、模型组、外泌体组和miR-122-5p转染外泌体组，后3组用刮宫+脂多糖双重损伤法构建宫腔粘连模型，术后第7天，正常组和模型组经尾静脉注射PBS，外泌体组和miR-122-5p转染外泌体组经尾静脉注射天然人脂肪间充质干细胞外泌体和miR-122-5p转染的人脂肪间充质干细胞外泌体。治疗第7天，各组随机取3只大鼠，分离子宫组织进行苏木精-伊红染色、Masson染色和免疫组化检测，每组剩余6只雌鼠按2∶1的比例与雄鼠合笼，合笼2周后观察大鼠胚胎着床位置和数量。
结果与结论：①miR-122-5p在宫腔粘连患者子宫内膜组织中低表达；②通过双重损伤法于术后第7天成功构建了SD大鼠宫腔粘连模型，与正常组相比，miR-122-5p在模型组子宫内膜中表达降低(P < 0.01)；③治疗7 d后，苏木精-伊红染色和Masson染色显示，与正常组相比，模型组大鼠子宫内膜厚度、腺体数量均显著降低，纤维化面积明显增加(P < 0.05)；与模型组相比，外泌体组和miR-122-5p转染外泌体组均能显著增加子宫内膜厚度、腺体数量并减少纤维化(P < 0.05)，且miR-122-5p转染外泌体组的治疗效果更加显著；④正常组、模型组、外泌体组、miR-122-5p转染外泌体组的妊娠率分别为100%，33.3%，66.7%，83.3%；模型组胚胎数量显著低于正常组(P < 0.05)，而miR-122-5p转染外泌体组胚胎数量高于模型组(P < 0.05)。结果表明，miR-122-5p转染的人脂肪间充质干细胞外泌体通过促进子宫内膜再生、抑制纤维化，有效改善宫腔粘连大鼠的生育能力。 
https://orcid.org/0009-0006-4304-4507(覃颖)；https://orcid.org/0009-0008-5065-6100(李红丽)；https://orcid.org/0000-0002-5179-8396(庞丽红)

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 宫腔粘连, 子宫内膜损伤, 子宫粘连, 子宫内膜纤维化, miR-122-5p, 脂肪间充质干细胞, 外泌体

Abstract: BACKGROUND: MicroRNAs, as important molecules regulating gene expression, play a crucial role in tissue repair. Exosomes, as promising drug carriers, have provided a new strategy for targeted therapy by delivering miRNAs. 
OBJECTIVE: To investigate the therapeutic effect of exosomes from adipose-derived mesenchymal stem cells overexpressing miR-122-5p on intrauterine adhesions in rats.
METHODS: Endometrial tissues were collected from patients with intrauterine adhesions and normal endometrial tissue from healthy individuals. The expression difference of miR-122-5p was detected by qPCR. miR-122-5p was transfected into human adipose-derived mesenchymal stem cells using lentiviral vectors, and exosomes were extracted using the 3D FloTrix viva Exo exosome harvesting system. Thirty-six female SD rats were randomly divided into normal group, model group, exosome group, and miR-122-5p-transfected exosome group. The latter three groups were used to establish a model of intrauterine adhesions using a double injury method of curettage and lipopolysaccharide. On day 7 after surgery, the normal group and the model group received PBS injection via the tail vein, while the exosome group and the miR-122-5p-transfected exosome group received natural exosomes and miR-122-5p-transfected exosomes from human adipose-derived mesenchymal stem cells via the tail vein, respectively. On day 7 of treatment, three rats were randomly selected from each group, and uterine tissues were isolated for hematoxylin-eosin staining, Masson staining, and immunohistochemical detection. The remaining six female rats in each group were caged with male rats at a ratio of 2:1. After two weeks of cohabitation, the implantation sites and numbers of embryos in the rats were observed.
RESULTS AND CONCLUSION: (1) miR-122-5p was lowly expressed in the endometrial tissue of patients with intrauterine adhesion (2) A dual-injury method was used to successfully establish a Sprague-Dawley rat intrauterine adhesion model on day 7 post-surgery. Compared with the normal group, the expression of miR-122-5p in the endometrial tissue of the model group was decreased (P < 0.01). (3) After 7 days of treatment, hematoxylin-eosin staining and Masson staining showed that, compared with the normal group, the endometrial thickness and gland number were significantly reduced, and the fibrotic area was significantly increased in the model group (P < 0.05). Compared with the model group, both the exosome group and the miR-122-5p transfected exosome group significantly increased endometrial thickness and gland number and reduced fibrosis (P < 0.05), and the therapeutic effect of the miR-122-5p transfected exosome group was more significant. (4) The pregnancy rates of the normal group, model group, exosome group, and miR-122-5p transfected exosome group were 100%, 33.3%, 66.7%, and 83.3%, respectively. The number of embryos in the model group was significantly lower than that in the normal group (P < 0.05), while the number of embryos in the miR-122-5p transfected exosome group was higher than that in the model group (P < 0.05). The results indicate that miR-122-5p-transfected human adipose-derived mesenchymal stem cell exosomes effectively improve the fertility of rats with intrauterine adhesions by promoting endometrial regeneration and inhibiting fibrosis.

Key words: intrauterine adhesions, endometrial injury, uterine adhesions, endometrial fibrosis, miR-122-5p, adipose-derived mesenchymal stem cells, exosomes

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