机械通气性肺损伤（ventilator-induced lung injury, VILI）是机械通气引起的最严重的并发症，目前治疗方法疗效有限，成为危重医学领域研究的难点。我们前期研究发现肺组织中存在一种新型间质细胞——特络细胞，能够诱导、促进干细胞的生长和分化，具有干细胞辅助细胞功能，且对肺微血管内皮细胞损伤具有修复作用，但其作用机制不明。近年来研究显示细胞外泌体是一种细胞之间交流的载体，参与组织修复过程。由此，我们提出假设：特络细胞可通过分泌的外泌体中miRNA对损伤的肺组织周围细胞发挥调节和修复作用。本课题拟分离特络细胞外泌体通过细胞损伤模型和机械通气性肺损伤小鼠模型探讨其对肺组织修复的作用机制。同时对比生理和病理条件下特络细胞外泌体miRNA表达谱差异，进步明确特络细胞外泌体在肺组织修复中的作用靶点和信号通路，为急性肺损伤的预防和治疗提供新的手段和方向。

Ventilator induced lung injury （VILI） is the most serious complications caused by mechanical ventilation. The mechanism of VILI is still not clear and lack of effective treatment, thus it’s a big challenge for research on critical care medicine. Our previous study showed that telocytes are interstitial cells to guide or nurse putative stem and progenitor cells in stem cell niches in lung. Telocytes may contribute to tissue repair and regeneration,but the mechanism is still not well-known. Our hypnosis is that telocytes-dervied exosomes（including miRNA,protein.etc) could regulate the regeneration of stem cell around the injury tissue. We plan to extract exosomes from lung telocytes and verify the regeneration function in culture cell and VILI mice model.In addition, the specific miRNA will be screened from lung telocytes-derived exsomes between physiological and pathological conditions.Furthermore,we will prove the function of specific miRNA in lung tissue repair. This study will be useful to clarify the biological function of telocytes-derived exsomes in lung repair and regeneration, as well as to provide new insights into the potential therapeutic values of exosomes in acute lung injury.

机械通气是治疗急性肺损伤或急性呼吸窘迫综合征等临床重症患者的重要手段，但可导致严重的并发症VILI。本研究旨在探讨特络细胞在小鼠机械通气性肺损伤中的作用及其可能的机制。研究将C57BL6小鼠，随机分为正常对照组；VILI组；TCs干预组。各组均进行湿干重比检测、H＆E染色并取BALF，BALF行白细胞计数、BCA试剂盒检测总蛋白含量、ELISA法检测TNF-α、IL-6及MIP-2的水平。在体外，用LPS处理TCs及小鼠EOMA，并用TCs的条件培养基对EOMA进行干预，用CCK8评价细胞的增殖率，用RT-PCR检测TCs中VEGF的mRNA含量，用ELISA检测TCs的培养基中VEGF含量。小鼠肺组织H＆E染色切片结果显示VILI组小鼠肺组织炎性细胞浸润增加，TCs干预组炎性细胞浸润情况减轻；ELISA结果显示VILI组小鼠BALF中TNF-α、IL-6及MIP-2含量增加，TCs干预组三种因子含量较VILI组降低；在体外，CCK8结果显示TCs的条件培养基可改善LPS可引起血管内皮细胞增殖率降低，RT-PCR及ELISA结果均提示LPS刺激后TCs中VEGF的表达增加。综上所述，TCs气道注射能减轻机械通气性肺损伤小鼠的肺部炎症反应，并可能通过增加VEGF的表达，促进肺血管内皮细胞增殖进而发挥对VILI的保护作用。