体外循环(CPB)能提供有效的呼吸循环支持，但可引发急性肺损伤(ALI)而导致严重后果。既往研究认为中性粒细胞主要通过释放蛋白酶及炎性介质引发ALI。近期在感染性疾病领域研究中发现：中性粒细胞通过形成胞外诱捕网(NETs)，发挥抗感染和组织损伤的双重作用。我们前期工作证实：CPB作为无菌性炎性刺激，亦可诱发NETs形成；并且发现幼稚粒细胞在细胞数量、趋化能力、NETs诱导和生成信号通路等方面，与成熟粒细胞存在差异，推测“幼稚中性粒细胞可能是CPB诱发NETs形成的主要细胞群体，在CPB相关ALI中发挥重要作用”。申请人拟在前期工作基础上，采用CPB大鼠模型，体内验证NETs在CPB相关ALI中的作用；在体外比较幼稚和成熟中性粒细胞形成NETs能力的差异，从NETs诱导和生成信号通路两方面探讨造成这种差异的分子机制，为临床预防和治疗CPB相关ALI提供理论依据和实验证据。

Although cardiopulmonary bypass (CPB) can provide effective respiratory support, it can also cause acute lung injury (ALI) and lead to serious consequences. Previous publications reported that neutrophils induce ALI mainly by releasing proteinases and inflammatory mediators. Recent studies in infectious diseases revealed that neutrophils play a dual role of anti-infection and tissue damage by forming the neutrophil extracellular traps (NETs). Our previous study demonstrated that CPB can also induce NETs formation as an aseptic inflammatory stimulation. Comparing with mature neutrophils, immature neutrophils are more likely to form NETs taking the advantages of cell quantity, chemotaxis and signaling pathways. We hypothesized that immature neutrophils might be the major cell source of induced by CPB and play an important role in the CPB related ALI. On the basis of our previous work, we proposed to testify the roles of NETs in CPB related ALI in vivo by using rat CPB model, and to compare the ability of NETs formation of immature and mature neutrophils in vitro. We aim to explore the molecular mechanism of such differences through the signaling pathways involving NETs induction and formation, and finally to provide theoretical basis and experimental evidence for clinical prevention and treatment of CPB related ALI.