外泌体在卵巢早衰诊治中的研究进展

doi:10.12280/gjfckx.20240378

摘要/Abstract

摘要：

卵巢早衰（premature ovarian failure，POF）是一种近年发病率逐渐升高的内分泌疾病，常导致女性生育力下降并伴随多种绝经后症状。目前POF病因暂不明确，治疗效果有限，迫切需要新的方法来改善卵巢功能，提高女性生育力。外泌体是一类携带多种活性物质的纳米囊泡，参与细胞间的信号传递，具有很强的靶向性和特异性。研究发现部分外泌体在正常组织与PDF组织中存在明显的差异性，可作为诊断POF的生物标志物。同时，外泌体也可通过作用于颗粒细胞、促进激素分泌、促进血管形成和抗氧化应激等方面在POF的治疗中起到重要作用。综述外泌体与POF关系的研究进展，以期为外泌体在POF中的研究提供一定的参考。

关键词: 原发性卵巢功能不全, 外泌体, 诊断, 治疗

Abstract:

Premature ovarian failure (POF) is an endocrine disorder with an increasing incidence in recent years, often leading to decreased female fertility and various postmenopausal symptoms. The etiology of POF remains unclear, and current treatment options are limited, necessitating new approaches to improve ovarian function and enhance fertility in affected women. Exosomes are nano-vesicles that carry a variety of active substances and participate in intercellular signal transmission, exhibiting strong targeting and specificity. Studies have revealed significant differences in certain exosomes between normal and PDF tissues, suggesting their potential as biomarkers for diagnosing POF. Additionally, exosomes may play a crucial role in POF treatment by affecting granulosa cells, promoting hormone secretion, angiogenesis, and combating oxidative stress. This review summarizes the research progress on the relationship between exosomes and POF, aiming to provide a reference for future studies on the role of exosomes in POF.

Key words: Primary ovarian insufficiency, Exosomes, Diagnosis, Therapy

郭佩仪, 朱雪红, 刘慧星, 陆丽妙, 林忠. 外泌体在卵巢早衰诊治中的研究进展[J]. 国际妇产科学杂志, 2024, 51(5): 492-496.

GUO Pei-yi, ZHU Xue-hong, LIU Hui-xing, LU Li-miao, LIN Zhong. Research Progress on Exosomes in the Diagnosis and Treatment of Premature Ovarian Failure[J]. Journal of International Obstetrics and Gynecology, 2024, 51(5): 492-496.

图/表 1

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提取技术		原理	优点	缺点	比较
离心法	①超速离心法	外泌体通过平衡沉降的原理进行分离，根据颗粒大小和密度施加不同的离心力	目前最常用的提取方法，提取到的标本量大，操作简单，费用相对较低	处理时间长，回收率和纯度低。提取出的外泌体对离心机的参数要求较高	a. 外泌体浓度：密度梯度离心法>超速离心法>超滤离心技术 b. 操作时间：密度梯度离心法>超速离心法>超滤离心技术^[16]
	②密度梯度离心法	根据离心力作用下不同沉降系数物质的分层分布分离外泌体	分离效果好，能保存好外泌体的活性，纯度相对较高	准备工作较为繁琐，操作复杂，设备要求高，耗时长，标本量少
	③超滤离心技术^[15]	可以在一定压力下让外泌体通过不同孔径膜的溶质来筛选	提取时间少，过程简单，外泌体回收率较高	外泌体的纯度和浓度较低，一些外泌体也可能黏附在滤膜上，导致产物损失和活性丧失
PEG沉淀法^[17]	PEG沉淀法	PEG与水分子结合后，在低速离心下使大量外泌体凝固沉淀，再用超速离心进行纯化	简单，产量大且外泌体的生物活性不受影响	易产生聚合物，影响数据准确性	与超速离心法相比，外泌体的产量可显著增加
免疫捕获法	①酶联免疫吸附分离法^[18] ②磁珠分离法	抗原抗体特异性吸附	特异性高，操作简单	分离的外泌体难以在后续实验中使用，并且获得的外泌体的活性容易受到影响	-
排阻色谱法^[19]	排阻色谱法	样品通过用凝胶填充的色谱柱，不同直径的粒子以不同的速率洗脱，这样就可以将外泌体与蛋白质、脂质等杂质分离开	操作简单、纯度高，可以保证外泌体的生物活性，适用于下游实验	耗时长，不能用于处理大量样品，色谱不可以重复使用	-

提取技术		原理	优点	缺点	比较
离心法	①超速离心法	外泌体通过平衡沉降的原理进行分离，根据颗粒大小和密度施加不同的离心力	目前最常用的提取方法，提取到的标本量大，操作简单，费用相对较低	处理时间长，回收率和纯度低。提取出的外泌体对离心机的参数要求较高	a. 外泌体浓度：密度梯度离心法>超速离心法>超滤离心技术 b. 操作时间：密度梯度离心法>超速离心法>超滤离心技术^[16]
	②密度梯度离心法	根据离心力作用下不同沉降系数物质的分层分布分离外泌体	分离效果好，能保存好外泌体的活性，纯度相对较高	准备工作较为繁琐，操作复杂，设备要求高，耗时长，标本量少
	③超滤离心技术^[15]	可以在一定压力下让外泌体通过不同孔径膜的溶质来筛选	提取时间少，过程简单，外泌体回收率较高	外泌体的纯度和浓度较低，一些外泌体也可能黏附在滤膜上，导致产物损失和活性丧失
PEG沉淀法^[17]	PEG沉淀法	PEG与水分子结合后，在低速离心下使大量外泌体凝固沉淀，再用超速离心进行纯化	简单，产量大且外泌体的生物活性不受影响	易产生聚合物，影响数据准确性	与超速离心法相比，外泌体的产量可显著增加
免疫捕获法	①酶联免疫吸附分离法^[18] ②磁珠分离法	抗原抗体特异性吸附	特异性高，操作简单	分离的外泌体难以在后续实验中使用，并且获得的外泌体的活性容易受到影响	-
排阻色谱法^[19]	排阻色谱法	样品通过用凝胶填充的色谱柱，不同直径的粒子以不同的速率洗脱，这样就可以将外泌体与蛋白质、脂质等杂质分离开	操作简单、纯度高，可以保证外泌体的生物活性，适用于下游实验	耗时长，不能用于处理大量样品，色谱不可以重复使用	-