携带miR-296-3p的脐带间充质干细胞来源外泌体改善妊娠期糖尿病模型大鼠症状

doi:10.16352/j.issn.1001-6325.2025.03.0310

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (3): 310-316.doi: 10.16352/j.issn.1001-6325.2025.03.0310

携带miR-296-3p的脐带间充质干细胞来源外泌体改善妊娠期糖尿病模型大鼠症状

赵丹¹, 刘廷翔², 郑楚文², 何文聪^1*

1.三峡大学第一临床医学院(宜昌市中心人民医院) 妇产科 & 三峡大学妇产科研究所,湖北宜昌 443003;
2.武汉北度生物科技有限公司,湖北武汉 430205

收稿日期:2024-08-06 修回日期:2024-11-01 发布日期:2025-02-25
通讯作者: ^*cong821201@126.com
基金资助:
2023年湖北省自然科学基金(指导性计划项目)(2023AFC018)

Exosomes derived from umbilical cord mesenchymal stem cells carryingmiR-296-3p improve symptoms of rat model with gestational diabetes mellitus

ZHAO Dan¹, LIU Tingxiang², ZHENG Chuwen², HE Wencong^1*

1. Department of Obstetrics and Gynecology, the First College of Clinical Medical Sciences(Yichang Central People′s Hospital), China Three Gorges University & Institute of Obstetrics and Gynecology, China Three Gorges University, Yichang 443003;
2. Wuhan Beidu Biotechnology Co. , Ltd. , Wuhan 430205, China

Received:2024-08-06 Revised:2024-11-01 Published:2025-02-25

摘要/Abstract

摘要： 目的探讨携带miR-296-3p的脐带间充质干细胞(MSCs)来源外泌体(Exo)对妊娠期糖尿病(GDM)大鼠血脂代谢及免疫功能的改善作用。方法用miR-296-3p-NC、miR-296-3p mimics转染MSCs后分别提取Exo,获得MSCs-Exo-miR-NC和MSCs-Exo-miR-296-3p;以RT-qPCR检测其中miR-296-3p表达,制备孕鼠后通过尾静脉注射链脲佐霉素来诱导建立GDM模型,随机分为模型组、MSCs-Exo-miR-NC组、MSCs-Exo-miR-296-3p组,每组10只,另外制备10只孕鼠为对照组;用MSCs-Exo-miR-NC和MSCs-Exo-miR-296-3p分组干预后检测各组孕鼠空腹血糖(FBG)、糖化血红蛋白(HbAlc)、母鼠与胎鼠质量、血脂4项、免疫器官指数;以ELISA测定其血清免疫球蛋白、免疫炎性因子水平;流式细胞测量术检测各组大鼠外周血T淋巴细胞免疫功能。结果与对照组相比,模型组大鼠母鼠和胎鼠质量、血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)、IL-6及IL-8水平、CD8⁺比例升高(P＜0.05),脾脏和胸腺指数、血清高密度脂蛋白(HDL-C)、IgA、IgG、IgM、IL-2及IL-10水平、CD4⁺比例降低(P＜0.05)。与模型组相比,MSCs-Exo-miR-NC组、MSCs-Exo-miR-296-3p组大鼠母鼠和胎鼠质量、血清TG、TC、LDL-C、IL-6及IL-8水平、CD8⁺比例降低(P＜0.05),脾脏和胸腺指数、血清HDL-C、IgA、IgG、IgM、IL-2及IL-10水平、CD4⁺比例升高(P＜0.05);且MSCs-Exo-miR-296-3p对GDM大鼠各指标的作用更强(P＜0.05)。结论携带miR-296-3p的MSCs来源Exo可改善GDM大鼠血脂代谢及免疫功能。

关键词: miR-296-3p, 脐带间充质干细胞, 外泌体, 妊娠期糖尿病, 免疫功能

Abstract: Objective To investigate the improvement of exosomes (Exo) derived from umbilical cord mesenchymal stem cells (MSCs) carrying miR-296-3p on blood lipid metabolism and immune function in gestational diabetes mellitus rats. Methods After transfection of MSCs with miR-296-3p-NC and miR-296-3p mimics, Exo was extracted to obtain MSCs-Exo-miR-NC and MSCs-Exo-miR-296-3p, respectively. RT-qPCR was used to detect the expressionof miR-296-3p; Pregnant mice were prepared and induced to establish a GDM model by tail vein injection of streptozotocin. Then they were randomly grouped into a model group, MSCs-Exo-miR-NC group, and MSCs-Exo-miR-296-3p group with 10 each. In addition, 10 pregnant mice were prepared as the control group. The weight of mother and fetal mice, four items of blood lipids and immune organ index in each group were measured after intervention with MSCs-Exo-miR-NC and MSCs-Exo-miR-296-3p. ELISA was applied to measure the level of serum immunoglobulin and immune inflammatory factors. Flow cytometry technology was applied to detect the immune function of peripheral blood T lymphocytes of rats in various groups, and their CD4⁺ and CD8⁺ values were compared. Results Compared with the control group, the maternal rat weight and fetal rat weight, serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), IL-6 and IL-8 levels and CD8⁺ ratio of rats in model group increased (P＜0.05), the spleen and thymus index, serum high-density lipoprotein (HDL-C), IgA, IgG, IgM, IL-2 and IL-10 levels and CD4⁺ ratio decreased (P＜0.05). Compared with the model group, the maternal rat weight and fetal rat weight, serum TG, TC, LDL-C, IL-6 and IL-8 level, and CD8⁺ ratio of rats from MSCs-Exo-miR-NC group and MSCs-Exo-miR-296-3p group decreased (P＜0.05), the spleen and thymus index, serum HDL-C, IgA, IgG, IgM, IL-2 and IL-10 levels and CD4⁺ ratio all increased (P＜0.05); MSCs-Exo-miR-296-3p had a stronger effect on various indicators of GDM rats (P＜0.05). Conclusions Exo derived from MSCs carrying miR-296-3p improves blood lipid metabolism and immune function of GDM rats.

Key words: miR-296-3p, umbilical cord mesenchymal stem cell, exosome, gestational diabetes mellitus, immune function

中图分类号:

R587.2

赵丹, 刘廷翔, 郑楚文, 何文聪. 携带miR-296-3p的脐带间充质干细胞来源外泌体改善妊娠期糖尿病模型大鼠症状[J]. 基础医学与临床, 2025, 45(3): 310-316.

ZHAO Dan, LIU Tingxiang, ZHENG Chuwen, HE Wencong. Exosomes derived from umbilical cord mesenchymal stem cells carryingmiR-296-3p improve symptoms of rat model with gestational diabetes mellitus[J]. Basic & Clinical Medicine, 2025, 45(3): 310-316.

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携带miR-296-3p的脐带间充质干细胞来源外泌体改善妊娠期糖尿病模型大鼠症状

Exosomes derived from umbilical cord mesenchymal stem cells carryingmiR-296-3p improve symptoms of rat model with gestational diabetes mellitus

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