隧道纳米管和线粒体转移在MSCs修复香烟诱导肺损伤中的作用及机制探讨

Chronic obstructive pulmonary disease is one of the most common respiratory diseases with high incidence and mortality, which lacks effective intervention. Recent researches have confirmed that mesenchymal stem cells attenuate cigarette-smoke induced emphysema and improve lung function. The discovery of tunneling nanotubes and mitochondrial transfer was a major breakthrough. A recent discovery has shown that intercellular communication using tunneling nanotubes can transfer mitochondria between mesenchymal stem cells and damaged cells, thereby resulting in the rescue of aerobic respiration and protection of lung cells from apoptosis. The role of mitochondrial transfer in MSCs intervention of CS induced lung injury need to be addressed. In this study, MSCs、lentivirus-Miro1-MSCs、siRNA-Miro1-MSCs are transplanted into rats with lung injury and mitochondrial transfer via tunneling nanotube-like structure is observed by means of flow cytometry and laser scanning confocal microscopy, the interrelation between paracrine and mitochondrial transfer are also discussed. Investigating the protective effects of MSCs might provide novel insights into the therapeutics of COPD.

慢性阻塞性肺病是临床常见的呼吸系统疾病之一，存在高发病率及高死亡率的特点，目前尚缺乏有效的干预与修复手段。动物试验已经证实骨髓间充质干细胞可减轻慢性阻塞性肺病大鼠的肺气肿改变，改善肺功能。线粒体转移是MSCs机制研究中的重大突破，研究表明MSCs可通过隧道纳米管样结构将MSCs中功能完好的线粒体转移至受损组织细胞，修复其线粒体功能，从而避免细胞凋亡及组织损伤。线粒体转移是否作为MSCs修复香烟所致肺损伤的主要机制是本研究需要解决的问题。本研究拟将MSCs、过表达Miro1的MSCs、SiRNA沉默Miro1的MSCs经气道注入肺损伤大鼠体内，通过流式及激光共聚焦显微镜技术观察隧道纳米管及线粒体转移，明确隧道纳米管及线粒体转移这一机制在MSCs干预减轻大鼠肺损伤中的作用以及其中的信号通路及调控机制，同时观察与旁分泌效应的相关性，为更系统、全面阐述骨髓间充质干细胞的作用机制提供依据。