中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (18): 4675-4684.doi: 10.12307/2026.746

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

卵巢早衰动物模型卵巢组织与卵巢早衰患者外周血中6种miRNAs的表达变化

王馨跃1，李红丽1，2，郭春辉1，陈继冰1，2，玉  华1，2   

  1. 1广西中医药大学，广西壮族自治区南宁市  530001；2广西中医药大学附属瑞康医院，广西壮族自治区南宁市  530011

  • 收稿日期:2025-06-16 接受日期:2025-09-11 出版日期:2026-06-28 发布日期:2025-12-06
  • 通讯作者: 玉华，硕士，硕士生导师，广西中医药大学附属瑞康医院产科，广西壮族自治区南宁市 530011；广西中医药大学，广西壮族自治区南宁市 530001
  • 作者简介:王馨跃，女，2000年生，辽宁省海城市人，汉族，医师，硕士，主要从事中西医结合妇科学研究。
  • 基金资助:
    广西重点研发计划项目(407312863109)，项目参与人：玉华；广西中医药大学2025年校级硕士研究生科研创新项目(YCSY2025071)，项目负责人：王馨跃

Changes in the expression of six microRNAs in ovarian tissue from animal models of premature ovarian failure and in peripheral blood of patients with premature ovarian failure

Wang Xinyue1, Li Hongli1, 2, Guo Chunhui1, Chen Jibing1, 2, Yu Hua1, 2   

  1. 1Guangxi University of Chinese Medicine, Nanning 530001, Guangxi Zhuang Autonomous Region, China; 2Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
  • Received:2025-06-16 Accepted:2025-09-11 Online:2026-06-28 Published:2025-12-06
  • Contact: Yu Hua, MS, Master’s supervisor, Guangxi University of Chinese Medicine, Nanning 530001, Guangxi Zhuang Autonomous Region, China; Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
  • About author:Wang Xinyue, MS, Guangxi University of Chinese Medicine, Nanning 530001, Guangxi Zhuang Autonomous Region, China
  • Supported by:
    Guangxi Key Research & Development Program Project, No. 407312863109 (to YH [project participant]); 2025 University-Level Master’s Student Scientific Research Innovation Project of Guangxi University of Chinese Medicine, No. YCSY2025071 (to WXY)

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摘要：


文题释义：
外泌体：是由细胞释放到细胞外基质中的膜结合囊泡，直径为40-200 nm。外泌体通过表面受体与靶细胞相互作用传递脂质、蛋白质等生物分子，从而调控靶细胞的生物学反应，不仅是细胞间信号传递的重要媒介，还可作为药物递送的载体。
microRNAs(miRNAs)：是一类长度为22-25个碱基的单链非编码RNA，广泛存在于真核生物中。miRNAs通过与靶基因结合抑制翻译或导致靶基因降解，从而在细胞生长、分化、发育和凋亡等多种生物过程中发挥重要的调控作用。
卵巢早衰：是一种妇科疾病，特征是40岁以下女性出现卵巢功能衰退、促卵泡生成素升高、雌激素水平与抗缪勒管激素水平降低等状况，并且伴有不同程度的围绝经期症状，是早发性卵巢功能不全中卵巢功能减退的最终阶段。

背景：研究表明，在大鼠卵巢早衰模型中呈现部分microRNAs(miRNAs)显著下调的表达特征，而这些miRNAs的过表达能够有效缓解卵巢早衰症状。因此，深入研究miRNAs作为潜在辅助生物标志物具有重要的学术价值和临床意义，可为卵巢早衰诊断提供更为稳定和可靠的参考依据。
目的：探究卵巢早衰动物模型卵巢组织与卵巢早衰患者外周血中6种miRNAs的表达变化是否具有一致性，验证6种miRNAs的临床诊断潜力。
方法：①将20只Wistar大鼠随机分为正常组(n=10)、卵巢早衰组(n=10)，卵巢早衰组通过腹腔注射顺铂[1 mg/(kg·d)，连续注射14 d]的方式建立卵巢早衰模型。造模结束后取材，ELISA法检测两组大鼠血清中促卵泡生成素、雌二醇、抗缪勒管激素水平，苏木精-伊红染色观察卵巢组织形态，Q-PCR检测卵巢组织中miR-10a-5p、miR-21-5p、miR-22-3p、miR-126-3p、miR-144-3p和miR-144-5p表达。②纳入10例卵巢早衰患者与10例健康对照女性，年龄均< 40岁，采用化学发光法检测两组受试者外周血中促卵泡生成素、雌二醇及抗缪勒管激素水平，Q-PCR检测外周血中miR-10a-5p、miR-21-5p、miR-22-3p、miR-126-3p、miR-144-3p和miR-144-5p表达。通过受试者工作特征曲线系统评估人类血液样本中6种miRNAs的效应量及诊断效能分析。
结果与结论：①与正常组相比，卵巢早衰组大鼠血清中促卵泡生成素水平升高(P < 0.05)，雌二醇和抗缪勒管激素水平下降(P < 0.05)。苏木精-伊红染色显示，与正常组相比，卵巢早衰组大鼠卵巢中卵泡数量明显减少。Q-PCR检测显示，与正常组相比，卵巢早衰组大鼠卵巢组织中miR-10a-5p、miR-21-5p、miR-22-3p、miR-126-3p、miR-144-3p和miR-144-5p表达均下调(P < 0.05)。②与健康对照组比较，卵巢早衰患者外周血中促卵泡生成素水平升高(P < 0.05)，雌二醇和抗缪勒管激素水平下降(P < 0.05)。Q-PCR检测显示，与健康对照组比较，卵巢早衰患者外周血中miR-10a-5p、miR-21-5p、miR-22-3p、miR-126-3p、miR-144-3p和miR-144-5p表达均下调(P < 0.05)。受试者工作特征曲线显示6种miRNAs均展现出优异的诊断区分能力(敏感性100%，特异性100%)，具备作为高特异性分子标志物的临床应用潜力。③结果表明，该6种miRNAs不仅可作为卵巢早衰的潜在生物标志物，还具备较高的临床诊断价值。

https://orcid.org/0009-0004-1355-5491(王馨跃)


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: 卵巢早衰, miRNAs, 外泌体, 细胞外囊泡, 外周血, 动物模型, 卵巢早衰患者, 组织构建

Abstract: BACKGROUND: Studies have demonstrated that specific microRNAs (miRNAs) exhibit significant downregulation in a rat model of premature ovarian failure, and their overexpression can effectively alleviate symptoms of premature ovarian failure. Therefore, investigating miRNAs as potential auxiliary biomarkers holds substantial academic and clinical significance, offering a more stable and reliable reference for the diagnosis of premature ovarian failure. 
OBJECTIVE: To investigate whether the expression patterns of six miRNAs in ovarian tissue from animal models of premature ovarian failure and in peripheral blood from patients with premature ovarian failure are consistent, and to validate the clinical diagnostic potential of these six miRNAs.
METHODS: (1) Twenty Wistar rats were randomly divided into a normal group (n=10) and a premature ovarian failure group (n=10). The model of premature ovarian failure was established in the premature ovarian failure group by intraperitoneal injection of cisplatin [1 mg/(kg·d)] for 14 continuous days. Following modeling, serum samples were collected from both groups. Levels of follicle-stimulating hormone, estradiol, and anti-Müllerian hormone were measured using ELISA. Ovarian tissue morphology was examined via hematoxylin-eosin staining. Q-PCR was used to detect the expression of miR-10a-5p, miR-21-5p, miR-22-3p, miR-126-3p, miR-144-3p, and miR-144-5p in ovarian tissue. (2) Ten patients with premature ovarian failure and ten healthy female controls, all aged < 40 years, were enrolled. Chemiluminescence assays measured the levels of follicle-stimulating hormone, estradiol, and anti-Müllerian hormone in peripheral blood from both groups. Q-PCR was used to detect the expression of miR-10a-5p, miR-21-5p, miR-22-3p, miR-126-3p, miR-144-3p, and miR-144-5p in peripheral blood. The effect size and diagnostic performance of these six miRNAs in human blood samples were systematically evaluated using receiver operating characteristic curves.
RESULTS AND CONCLUSION: (1) Compared with the normal group, rats with premature ovarian failure showed significantly elevated follicle-stimulating hormone level and reduced estradiol and anti-Müllerian hormone levels. Hematoxylin-eosin staining revealed a significant decrease in the number of follicles in the ovaries of rats with premature ovarian failure compared with the normal group. The expression of miR-10a-5p, miR-21-5p, miR-22-3p, miR-126-3p, miR-144-3p, and miR-144-5p was markedly downregulated in the ovaries of rats with premature ovarian failure compared with the normal group (P < 0.05). (2) Compared with healthy controls, patients with premature ovarian failure exhibited elevated levels of follicle-stimulating hormone in peripheral blood (P < 0.05), along with decreased levels of estradiol and anti-Müllerian hormone (P < 0.05). Q-PCR assay revealed that, compared with healthy controls, patients with premature ovarian failure exhibited downregulated expression of miR-10a-5p, miR-21-5p, miR-22-3p, miR-126-3p, miR-144-3p, and miR-144-5p in peripheral blood (P < 0.05). The receiver operating characteristic curves demonstrated that all six miRNAs exhibited excellent diagnostic discrimination capabilities (sensitivity: 100%, specificity: 100%), indicating their clinical potential as highly specific molecular biomarkers for premature ovarian failure. These findings indicate that these six miRNAs may serve not only as promising biomarkers for premature ovarian failure but also as clinically valuable tools.


Key words: premature ovarian failure;, miRNAs, exosomes, extracellular vesicles, peripheral blood, animal model, patients with premature ovarian failure, tissue construction

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