间充质干细胞来源的外泌体携带ANXA1改善ARDS肺血管通透性的实验研究

Acute respiratory distress syndrome (ARDS) is a common complication of burn and trauma, associated with increased pulmonary vascular permeability. Evidence exists that mesenchymal stem cells-derived exosomes (ExosMSCs) can inhibit the increase of vascular permeability. However, the specific mechanism has not been fully elucidated. Previous studies reported that annexin A1 (ANXA1) was involved in the regulation of vascular permeability through formyl peptide receptor (FPR). Our preliminary experiments showed that ANXA1 existed in ExosMSCs, and upregulation of ANXA1 in ExosMSCs could attenuate lung edema formation and reduce pulmonary vascular leakage. The contents of this project include: 1. To demonstrate that i.v. injection of ExosMSCs could prevent pulmonary inflammation, edema and blood vessel hyperpermeability in mouse model of lung injury. 2. To determine if ANXA1 carried by ExosMSCs could constrain vascular permeability by interacting with FRR. 3. To elucidate the signaling mechanisms by which ExosMSCs modulate endothelial cell-cell junctions. The results of this project will further reveal the therapeutic mechanisms of ExosMSCs and provide a new theoretical basis and measures for the treatment of ARDS.

烧（创）伤患者常并发急性呼吸窘迫综合征（ARDS），以肺血管通透性增高为其病理特征。间充质干细胞（MSCs）分泌的外泌体（ExosMSCs）可抑制血管通透性增高，但调控机制不完全清楚。研究证实，膜联蛋白A1（ANXA1）可通过甲酰肽受体（FPR）参与调控血管通透性。预实验发现ExosMSCs含膜联蛋白A1，上调后可有效可改善肺水肿及肺血管渗出。本课题研究内容包括：①观察肺损伤小鼠静脉注射ExosMSCs后肺炎症、水肿情况及肺血管通透性；②证实ExosMSCs通过其携带的膜联蛋白A1作用于FPR调控肺血管内皮细胞通透性；③探索ExosMSCs调控肺血管内皮细胞间连接蛋白所涉及的信号通路。本课题将进一步揭示ExosMSCs改善ARDS肺血管通透性的作用及其机制，为ARDS的治疗提供新的理论依据和治疗措施。

烧（创）伤患者常并发急性呼吸窘迫综合征（ARDS），以肺血管通透性增高为其病理特征。间充质干细胞（MSCs）分泌的外泌体（ExosMSCs）可抑制血管通透性增高，但调控机制不完全清楚。研究证实，膜联蛋白A1（ANXA1）可通过甲酰肽受体（FPR）参与调控血通透性。预实验发现ExosMSCs含膜联蛋白A1，上调后可有效可改善肺水肿及肺血管渗出。本课题研究内容包括：①观察肺损伤小鼠静脉注射ExosMSCs后肺炎症、水肿情况及肺血管通透性；②证实ExosMSCs通过其携带的膜联蛋白A1作用于FPR调控肺血管内皮细胞通透性；③探索ExosMSCs调控肺血管内皮细胞间连接蛋白所涉及的信号通路。本课题将进一步揭示ExosMSCs改善ARDS肺血管通透性的作用及其机制，为ARDS的治疗提供新的理论依据和治疗措施。