01

        细胞外囊泡

        肺是人体中血管密度最高的器官。因此，肺内皮细胞显著促进包括外泌体、微囊泡和凋亡小体的细胞外囊泡(EVs)循环。除内皮外，EVs还有可能来自肺泡巨噬细胞、纤维细胞和上皮细胞。由于EVs包裹载体分子，例如miRNA、mRNA和蛋白质，因此这些细胞间的通讯器有助于深入了解供体细胞的健康和疾病状况，实现生物体内细胞之间或物种之间的通讯[1，2]，并可作为肺部疾病进展的有用生物标记;此外，并非细胞分泌的所有囊泡都有功能或在某种生物过程中起作用。

        02

        分 类

        一些研究将EVs分为两大类：I)外泌体，定义为通过多囊体的胞吐作用释放囊泡;II)囊泡，定义为由质膜组装和释放的囊泡[3]。

        然而，最近的研究根据囊泡的大小及其形成方式将EVs分为外泌体、微囊泡、微粒或凋亡小体[4-10]。

        1. 外泌体

        是一种小的EVs，直径范围在30～150 nm之间，起源于几乎所有细胞类型多囊体(MVB)的内囊泡。典型的外泌体被磷脂膜包围，该膜含有其细胞起源特征的脂质[11，12]，具有高水平的胆固醇、鞘磷脂、神经酰胺和耐洗涤剂的膜结构域(脂质筏)[13，14]。外泌体的另一个显著特征是四跨膜蛋白的存在，包括CD9、CD63、CD81和CD82 [15]。大量研究表明，外泌体中存在核酸载体[15-18]，在受体细胞中释放具有功能活性。

        2. 微囊

        微囊(MVs)或微粒(MPs)(50～1000 nm)是通过活细胞的质膜直接向外发芽并释放膜微绒毛而分泌的[19，20]。

        3. 凋亡小体

        凋亡小体(也称为“凋亡水泡”或“凋亡囊泡”)代表在细胞凋亡过程中由质膜的向外发芽、起泡或破裂而释放的EV类型。当这些囊泡被抗原提呈细胞或被邻近细胞摄取时，可能导致抗炎或耐受性反应[21-23]。

        03

        EVs在肺部疾病发病机理中的作用

        表1 各种肺部并发症中潜在的细胞外囊泡标志物

        *内皮衍生MP(EMP)，血小板来源MP(PMP)，白细胞来源MP(LMP)

        04

        EVs在肺部疾病中的治疗潜力

        05

        总 结

        总之，EVs是新兴的多种肺部疾病的重要组成部分。很明显，EVs代表了一个异质种群，其组成和载体都大不相同。EVs是一个快速发展的领域，用于EVs的分离和分类方法仍然缺乏统一性。例如，肺癌的许多亚型在分子病理学、治疗和预后方面均存在差异[77]。这种异质性对于几乎所有的肺部疾病都是确实存在的，将来评估EVs作为生物标志物和治疗药物的研究应该诠释阐明这些差异。这一有应用前景的研究领域预计可为数以百万计遭受肺部疾病折磨的患者带来希望，尽管这些疾病采用当今的标准治疗方法仍无法治愈。

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        目前研究表明细胞外囊泡在哮喘、慢性阻塞性肺病、急性肺损伤/急性呼吸窘迫综合征等肺部炎症性疾病的发展中发挥重要作用并具有潜在的治疗价值。

        MCC号Xo920082044有效期2021-08-17，资料过期，视同作废。