肺巨噬细胞不能有效清除病原体，促进脓毒症肺损伤的发生发展。具有胶原结构的巨噬细胞受体（macrophage receptor with collagenous structure，MARCO）为A类清道夫受体成员，主要表达于巨噬细胞，介导非调理素依赖的微粒和细菌的吞噬，在先天宿主防御系统中发挥重要作用。我们前期研究证实：在脓毒症肺损伤模型中肺巨噬细胞去乙酰化酶2（SIRT2）、MARCO表达增加；干预SIRT2表达后，脓毒症肺损伤减轻，肺泡巨噬细胞对铜绿假单胞菌的吞噬能力增强；同时，SIRT2抑制肺巨噬细胞MARCO的表达。因此我们假设：SIRT2通过调控肺巨噬细胞MARCO的表达水平，影响肺巨噬细胞吞噬功能，参与脓毒症肺损伤的发生发展。本项目拟采用基因敲除动物模型、腺病毒RNA干扰等技术平台，从整体、细胞、分子水平阐明SIRT2调控肺巨噬细胞MARCO在脓毒症肺损伤中的作用及其分子机制。

The disturbance of function in pulmonary macrophages, such as inefficiency of clearing pathogens, would directly exacerbate and mediate the initiation and development of lung injury induced by sepsis. Macrophage receptor with collagenous structure is a members of class A scavenger receptors, mainly expressed on macrophages and has an important role in innate host defense via regulating the phagocytosis of particles and bacterias. Our preliminary studies have shown that the level of sirtuin 2(SIRT2) and MARCO mRNA increased in the pulmonary macrophages that were isolated form the mouse model of sepsis-induced lung injury, and interfering with SIRT2 expression significantly alleviated sepsis-induced lung tissue injury and enhanced the phagocytosis of Pseudomonas aeruginosa by alveolar macrophages, meanwhile, SIRT2 could inhibit the expression of MARCO on pulmonary macrophages. Therefore, we hypothesize that SIRT2 will be involved in the pathogenesis of sepsis-induced lung injury via regulating the expression of MARCO on pulmonary macrophages. The present project will aim to identify the functional role and molecular mechanism of SIRT2 in sepsis-induced lung injury.