聚多巴胺调控中性粒细胞迁移和凋亡对急性肺损伤干预的作用及机制

Acute lung injury (ALI)/Acute respiratory distress syndrome (ARDS) is a life-threatening lung disease. Effective prevention and treatment of ALI is an important problem to be solved urgently. Neutrophils trapped in the lung tissue and result in severe lung tissue injury by releasing reactive oxygen (ROS). In our preliminary study, we found that nanomaterial polydopamine (PDA) could effectively clear the ROS and exert protective effects in a mouse model of ALI; further study showed that PDA could inhibit the migration of the polymorphonuclear neutrophils (PMNs) into the lung tissue, thereby resulting in the abnormal accumulation of the PMN in the lung tissue; moreover, PDA could result in the persistent activation of the PMN by increasing the PMN apoptosis. However, the detailed mechanisms have not been explored. Based on these preliminary data, our project plan to discuss the protective effect of nanomaterial PDA in a ALI mouse model, and explore the mechanism based on the in vitro assay of neutrophil migration and apoptosis; finally PDA will be used as the in vivo therapeutic method to observe its treatment efficacy in the ALI. The achievements of this project may provide a new treatment method for acute lung injury.

急性肺损伤(ALI)/急性呼吸窘迫综合症(ARDS)是一种严重威胁生命的肺部疾病，有效的防治ALI是目前临床亟待解决的重要问题。业已表明，中性粒细胞在肺组织积聚释放大量活性氧(ROS)造成肺组织严重损伤。我们前期研究发现：纳米材料聚多巴胺(PDA)能够有效的清除ROS，对急性肺损伤小鼠具有有效的保护作用，进一步研究发现PDA可抑制中性粒细胞(PMN)向肺组织迁移从而减少PMN在肺组织的异常聚集。此外，PDA还能促进PMN的凋亡防止PMN的持续激活，但确切的机制尚待研究。本项目以此为切入点通过急性肺损伤小鼠模型来探讨纳米材料PDA在ALI中的保护作用，进而通过体外实验阐明PDA调控中性粒细胞的迁移、趋化及凋亡参与ALI疾病进程的作用机制，最后将PDA作为体内干预手段，观察PDA是否可以用于急性肺损伤安全有效的治疗。本项目所获研究成果以期为临床急性肺损伤的干预治疗提供一种新手段。

急性肺损伤(ALI)/急性呼吸窘迫综合症(ARDS)是一种严重威胁生命的肺部疾病，有效的防治ALI是目前临床亟待解决的重要问题。业已表明，中性粒细胞在肺组织积聚释放大量活性氧(ROS)造成肺组织严重损伤。本项目通过急性肺损伤小鼠模型来探讨纳米材料PDA在ALI中的保护作用，进而通过体外实验阐明PDA调控中性粒细胞的迁移、趋化及凋亡参与ALI疾病进程的作用机制，最后将PDA作为体内干预手段，观察PDA治疗急性肺损伤的安全有性。. 本研究制作了PDA纳米颗粒作为治疗性纳米药物，不仅可以保护组织免受活性氧损伤，而且可以调节失调的中性粒细胞的行为，改善急性炎症反应。这一作用不仅可以显著改善ALI的临床表现，还可以显著改善伴有中性粒细胞失调的其他炎性疾病，如急性呼吸窘迫综合征、急性痛风性肝病、癫痫等。本研究为纳米药物在抗炎治疗中的应用提供了广阔前景，为临床急性肺损伤的干预治疗提供一种新手段。