间充质干细胞及其外泌体在治疗ALI/ARDS中的机制研究进展  

Research progress on the mechanism of mesenchymal stem cells and their derived exosomes in the treatment of ALI/ARDS

作　　者：丁洪波 季晓珍 许永安[1] Ding Hongbo;Ji Xiaozhen;Xu Yongan(Department of Emergency Medicine,the Second Affiliated Hospital,Zhejiang University School of Medicine,Emergency Medicine Institute of Zhejiang University,Key Laboratory of the Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province,Zhejiang Province Clinical Research Center for Emergency and Critical Care Medicine,Hangzhou 310009,China)

机构地区：[1]浙江大学医学院附属第二医院急诊医学科、浙江大学急救医学研究所、浙江省严重创伤与烧伤诊治重点实验室、浙江省急危重症临床医学研究中心,浙江杭州310009 [2]龙泉市人民医院,浙江龙泉323700

出　　处：《中国急救医学》2024年第6期548-552,F0003,共6页Chinese Journal of Critical Care Medicine

基　　金：国家自然科学基金(81571916,81372079,81201478);浙江省重点研发项目(2024C03186);国家-浙江省中医药管理局共建重大项目(GZY-ZJ-KJ-24030)。

摘　　要：间充质干细胞(MSC)因其显著的免疫调节能力及再生能力,已在多种疾病的细胞治疗领域显示出巨大前景,特别是在急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)的治疗中表现出极高的应用潜力。ALI/ARDS均为严重的肺部炎症状态,常导致高病死率。MSC能通过分泌MSC来源的外泌体(MSC-EXO)——一种富含蛋白质、RNA及其他生物分子的微小囊泡发挥其治疗效应。在ALI/ARDS治疗中,MSC-EXO通过多种信号通路发挥作用,包括抑制核转录因子-κB(NF-κB)通路以降低炎症反应,激活磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)通路促进细胞存活,及调节丝裂原活化蛋白激酶(MAPK)与酪氨酸蛋白激酶/信号转导与转录激活子(JAK/STAT)通路以支持肺组织的修复和再生等。因此,MSC和MSC-EXO的研究与应用不仅开辟了新的治疗策略,也为深入理解ALI/ARDS的复杂病理生理机制提供了重要视角。Mesenchymal stem cells(MSCs),due to their remarkable immunomodulatory abilities and regenerative potential,have shown great prospects in the field of cell therapy for various diseases,especially exhibiting high application potential in the treatment of acute lung injury(ALI)and acute respiratory distress syndrome(ARDS).Both diseases are severe inflammatory conditions of the lungs that often lead to high mortality rates.MSCs exert their therapeutic effects by secreting extracellular vesicles known as mesenchymal stem cell-derived exosomes(MSC-EXOs)——tiny bubbles rich in proteins,RNA,and other biomolecules.In the treatment of ALI/ARDS,MSC-EXOs produce a marked effect through multiple signaling pathways,including but not limited to inhibiting the nuclear factor-κB(NF-κB)pathway to reduce inflammatory responses,activating the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)pathway to promote cell survival,and modulating the mitogen activated protein kinase(MAPK)and Janus kinase/signal transducer and activator of transcription(JAK/STAT)pathways to support the repair and regeneration of lung tissue.Therefore,research and application of MSCs and MSC-EXOs not only pave the way for new therapeutic strategies but also provide a significant perspective for a deeper understanding of the complex pathophysiology of ALI/ARDS.

关 键 词：间充质干细胞 外泌体 急性肺损伤 急性呼吸窘迫综合征 信号通路 核转录因子-ΚB 丝裂原活化蛋白激酶 酪氨酸蛋白激酶 

分 类 号：R563[医药卫生—呼吸系统]