脓毒症肺损伤为严重威胁健康的重大疾病之一，在老年人高发，归因于免疫衰老，但确切机制不明，也缺乏有效防治手段。近来研究认为它与中性粒细胞胞外诱捕网（NETs）形成失调有关。本课题组前期发现老年小鼠易发生脓毒症肺损伤，其机制与衰老致ATG5表达下调介导NETs形成缺陷有关。p73为调控ATG5转录激活的上游基因，我们前期初步发现它具有衰老相关性的表达下调，但在脓毒症中的免疫调节作用尚无报道。据此我们推出假说：中性粒细胞p73基因表达失调致自噬相关NETs形成缺陷是老年脓毒症肺损伤的重要发病机制。为验证该假说，拟首先进一步阐明NETs形成缺陷与脓毒症肺损伤的关系；然后在细胞和动物水平通过基因敲减和过表达等手段探讨NETs形成缺陷的p73基因调节机制；最后在老年脓毒症小鼠及其中性粒细胞上行活化p73的药物干预，验证其疗效。本研究有望阐明老年脓毒症肺损伤的发病机制和防治策略，为改善其预后提供新思路。

Septic lung injury is of high incidence in the elderly. The insufficiency in the understanding of its mechanisms and the lack of effective prevention and management made it one of the most serious diseases. Recently researchers found that septic lung injury is related to the dysregulation of neutrophil extracellular traps (NETs). Our previous studies revealed that the defect in NETs formation mediated by aging related down-regulation of ATG5 participated in the occurrence of lung injury in aged mice. P73 is the upstream gene that regulates the transcription and activation of ATG5. We found a down-regulated pattern of p73 with aging, but no report on its role during infection. Accordingly, we propose a hypothesis that the imbalanced NETs caused by p73 is important in the pathogenesis of lung injury in the elderly. This study consists of three parts: (1) to further clarify the interaction between NETs deficiency and septic lung injury; (2) to investigate the mechanism by which p73 regulates NETs formation both in vitro and in vivo; (3) to verify the therapeutic effect of potential p73 regulator (curcumin) in mice with septic lung injury. This study is expected to shed light on the pathogenesis and preventive strategy of septic lung injury in the elderly.