Abstract：
Preterm premature rupture of membranes (pPROM) is a common pregnancy disease closely related to inflammation. The formyl peptide receptor 2 (FPR2), a member of the G protein-coupled receptor family involved in defense responses, inflammation, and disturbances in glucose and lipid metabolism, is associated with pregnancy diseases. Lipoxin A4 (LXA4) can activate FPR2 and inhibit the inflammatory signals. Exosomes derived from mesenchymal stem cells are good materials for anti-inflammatory and tissue repair. This study aims to investigate the anti-inflammatory and tissue repair effects of the combined application of exosomes derived from human umbilical cord mesenchymal stem cells and FPR2 agonist LXA4. In this study, LPS was used to establish the inflammation model of pregnant mice and HTR8 cells, and LXA4 and exosome treatment were carried out to observe the fetal membranes\' tissue repair. The scanning and transmission electron microscopy of fetal membrane tissue indicated that the structure of pPROM tissue was disordered, and the cell gap was significantly increased. The results of the inflammatory mice model suggested that LPS can cause damage to the fetal membrane structure. LXA4 combined with exosome treatment can inhibit the production of MMP2 and MMP9, and promote neovascularization by inhibiting the p38 MAPK/Nuclear factor kB p65 (NFkB) pathway in the inflammation model of HTR8 cells and pregnant mice, thus helping to control inflammation and tissue repair.
摘要：
未足月胎膜早破(pPROM)是一种与炎症密切相关的常见妊娠疾病。甲酰肽受体2（FPR2），参与防御反应的G蛋白偶联受体家族成员，炎症,以及葡萄糖和脂质代谢紊乱，与妊娠疾病有关。脂氧素A4（LXA4）可以激活FPR2并抑制炎症信号。间充质干细胞来源的外泌体是抗炎和组织修复的良好材料。本研究旨在探讨人脐带间充质干细胞外泌体与FPR2激动剂LXA4联合应用的抗炎和组织修复作用。在这项研究中,用LPS建立孕鼠和HTR8细胞的炎症模型,进行LXA4和外泌体处理以观察胎膜组织修复。胎膜组织的扫描和透射电镜显示pPROM组织结构紊乱,细胞间隙显著增大。炎症小鼠模型的结果提示LPS可引起胎膜结构的损伤。LXA4联合外泌体治疗可通过抑制HTR8细胞和孕鼠炎症模型中p38MAPK/核因子kBp65（NFkB）通路抑制MMP2和MMP9的产生，促进新生血管的形成，从而帮助控制炎症和组织修复。
