中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (14): 3626-3635.doi: 10.12307/2026.046

• 水凝胶材料Hydrogel materials • 上一篇    下一篇

miR-424-5p修饰外泌体/泊洛沙姆407水凝胶修复大鼠子宫内膜损伤

孔小娟1，2，谈珍瑜2，雷  磊1   

  1. 1湖南中医药大学，湖南省长沙市   410000；2湖南中医药大学第一附属医院妇产科，湖南省长沙市   410000
  • 收稿日期:2025-03-01 接受日期:2025-05-12 出版日期:2026-05-18 发布日期:2025-09-11
  • 通讯作者: 雷磊，博士，主任医师，湖南中医药大学，湖南省长沙市 410000
  • 作者简介:孔小娟，女，1977年生，河南省南阳市人，汉族，硕士，副主任医师，主要从事妇产科研究。
  • 基金资助:
    湖南中医药大学院校联合基金项目(2024XYLH350)，项目负责人：孔小娟；湖南创新型省份建设专项(2025JJ80931)，项目负责人：孔小娟

Repair of rat endometrial injury by using miR-424-5p modified exosome/Poloxam 407 hydrogel

Kong Xiaojuan1, 2, Tan Zhenyu2, Lei Lei1   

  1. 1Hunan University of Chinese Medicine, Changsha 410000, Hunan Province, China; 2Department of Obstetrics and Gynecology, The First Hospital of Hunan University of Chinese Medicine, Changsha 410000, Hunan Province, China
  • Received:2025-03-01 Accepted:2025-05-12 Online:2026-05-18 Published:2025-09-11
  • Contact: Lei Lei, MD, Chief physician, Hunan University of Chinese Medicine, Changsha 410000, Hunan Province, China
  • About author:Kong Xiaojuan, MS, Associate chief physician, Hunan University of Chinese Medicine, Changsha 410000, Hunan Province, China; Department of Obstetrics and Gynecology, The First Hospital of Hunan University of Chinese Medicine, Changsha 410000, Hunan Province, China
  • Supported by:
    University Joint Fund Project of Hunan University of Chinese Medicine, No. 2024XYLH350 (to KXJ); Hunan Innovative Province Construction Special Project, No. 2025JJ80931 (to KXJ)

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摘要：

文题释义：
外泌体：是大多数细胞分泌的微小膜泡，具有脂质双层膜，直径为30-150 nm。外泌体能够参与细胞通讯与物质交换，影响细胞的生理状态并与多种疾病的发生与进程密切相关。
MicroRNA(miRNA)：是一种非编码的小RNA，能够靶向结合mRNA的3’非翻译区并抑制其翻译，或者与翻译区结合降低信息的传导。

背景：研究表明，外泌体与miR-424-5p模拟物可促进血管生成并改善子宫内膜损伤，但通过宫腔给药后外泌体很难附着于子宫内膜壁上，缩短了外泌体保留时间，导致外泌体不能充分发挥生物学效应。因此，近年来多采用生物支架材料递送外泌体，使外泌体在损伤部位持续发挥生物学效应。
目的：观察miR-424-5p修饰外泌体/泊洛沙姆407水凝胶对人脐静脉内皮细胞增殖、迁移与成血管的影响，以及在大鼠子宫内膜损伤中的治疗作用。
方法：通过慢病毒转染的方法将miR-424-5p转染至大鼠骨髓间充质干细胞中，随后从骨髓间充质干细胞上清液中提取外泌体并进行鉴定。采用RT-qPCR检测未转染组、转染慢病毒组及转染空载体组外泌体中miR-424-5p表达，以验证转染成功。分别制备泊洛沙姆407水凝胶、外泌体/泊洛沙姆407水凝胶、miR-424-5p修饰外泌体/泊洛沙姆407水凝胶，与人脐静脉内皮细胞共培养后检测细胞增殖、迁移与毛细血管网形成情况。将35只SD大鼠随机分为假手术组、模型组、水凝胶组、未转染外泌体水凝胶组、转染外泌体水凝胶组，每组7只，除假手术组外，其余4组建立子宫内膜损伤模型，并给予对应的水凝胶治疗，模型组不进行治疗。术后14 d取材，进行子宫内膜形态结构、血管生成与容受性指标检测。
结果与结论：①体外细胞实验结果显示，外泌体/泊洛沙姆407水凝胶、miR-424-5p修饰外泌体/泊洛沙姆407水凝胶均可促进人脐静脉内皮细胞的增殖、迁移与毛细血管网形成，并且miR-424-5p修饰外泌体/泊洛沙姆407水凝胶的促进作用更显著；②动物实验结果显示，外泌体/泊洛沙姆407水凝胶、miR-424-5p修饰外泌体/泊洛沙407水凝胶可增加子宫内膜的厚度与腺体数量，抑制纤维化，促进血管形成及容受性指标的表达，对子宫内膜损伤均具有良好的治疗作用，并且miR-424-5p修饰外泌体/泊洛沙407水凝胶的治疗作用更加显著。结果表明，miR-424-5p修饰外泌体/泊洛沙姆407水凝胶可促进人脐静脉内皮细胞的增殖、迁移与成血管，以及促进大鼠损伤子宫内膜的组织再生、血管形成并改善容受性，发挥潜在的治疗作用。
https://orcid.org/0009-0005-2625-1187(孔小娟)

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料；口腔生物材料；纳米材料；缓释材料；材料相容性；组织工程

关键词: 外泌体, 水凝胶, 慢病毒转染, 泊洛沙姆407, 子宫内膜损伤, 人脐静脉内皮细胞

Abstract: BACKGROUND: Studies have shown that treatment with exosomes and miR-424-5p mimics can promote angiogenesis and ameliorate endometrial injury. However, it is difficult for exosomes to attach to the endometrial wall after intrauterine administration, which shortens the retention time of exosomes and results in the inability of exosomes to fully exert their biological effects. Therefore, in recent years, more and more biological scaffolds have been used to deliver exosomes, so that exosomes can continue to play biological effects at the injured site.
OBJECTIVE: To observe the effect of miR-424-5p modified exosome/Poloxam 407 hydrogel on the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells, as well as the therapeutic effect on endometrial injury in rats. 
METHODS: miR-424-5p was transfected into rat bone marrow mesenchymal stem cells by lentiviral transfection, and exosomes were subsequently extracted from bone marrow mesenchymal stem cells and identified. The expression of miR-424-5p in exosomes not transfected with lentivirus, exosomes transfected with lentivirus, and exosomes transfected with empty vector were detected by RT-qPCR to verify the transfection success. Poloxam 407 hydrogel, exosome/Poloxam 407 hydrogel, and miR-424-5p modified exosome/Poloxam 407 hydrogel were prepared respectively, and cell proliferation, migration, and capillary network formation were detected after co-culture with human umbilical vein endothelial cells. A total of 35 SD rats were randomly divided into sham operation group, model group, hydrogel group, non-transfected exosome hydrogel group, and transfected exosome hydrogel group, with 7 rats in each group. Except the sham operation group, endometrial injury models were established in the other four groups and corresponding hydrogel treatment was given, while no treatment was given in the model group. At 14 days after operation, samples were collected. The morphologic structure, angiogenesis, and receptivity indexes of endometrium were detected.
RESULTS AND CONCLUSION: (1) In vitro cell experiment results showed that both exosome/Poloxam 407 hydrogel and miR-424-5P-modified exosome/Poloxam 407 hydrogel could promote the proliferation, migration, and capillary network formation of human umbilical vein endothelial cells, and the promotion effect of miR-424-5p-modified exosome/Poloxam 407 hydrogel was more significant. (2) Animal experiments showed that exosome/Poloxam 407 hydrogel and miR-424-5p modified exosome/Poloxam 407 hydrogel could increase the thickness and number of glands of the injured endometrial, inhibit fibrosis, promote the formation of blood vessels, and the expression of tolerance indicators, and have a good therapeutic effect on endometrial injury. Moreover, miR-424-5p modified exosome/Poloxa 407 hydrogel had a more significant therapeutic effect. These findings conclude that miR-424-5p modified exosome/Poloxam 407 hydrogel can promote tissue regeneration, angiogenesis and improve receptivity of injured endometrium in rats by promoting the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells, thus playing a potential therapeutic role. 

Key words: exosome, hydrogel, lentivirus transfection, Poloxam 407, endometrial injury, human umbilical vein endothelial cell

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