早产儿高氧肺损伤机制涉及P53介导的肺泡上皮细胞（AEC）凋亡。研究显示，当SIRT1在翻译后水平发生SUMO化修饰并定位于细胞核后获得去乙酰化酶活性，可去乙酰化P53抑制细胞凋亡。但我们对II型AEC的研究却发现似乎矛盾的结果：高氧暴露后细胞内SIRT1增加（翻译水平），但P53去乙酰化减少。另有文献报道，SIRT1翻译后水平的去SUMO化修饰可抑制其酶活性。结合文献和前期研究，我们推测高氧暴露II型AEC中存在调节SIRT1活性的翻译后机制，SIRT1的去SUMO修饰是早产儿高氧肺损伤中P53的上游调节因素。本项目以早产儿、高氧暴露新生动物及细胞模型为研究载体，采用基因敲除/沉默、Western blot、激光共聚焦及液相串联质谱等技术，从人群、组织、细胞及分子水平验证这一假说，阐明SIRT1 SUMO化修饰在早产儿高氧肺损伤发生机制中的作用，为支气管肺发育不良的早期干预提供新的靶点。

The mechanism of preterm hyperoxia lung injury involved in the apoptosis of alveolar epithelial cells (AEC) which induced by P53. After being sumoylated at post-translation level and located in the nucleus, human sirtuin 1 (SIRT1) had deacetylase activity and could inhibit cell apoptosis by deacetylating P53. Our previous study found a seemingly paradox result that SIRT1 increased at the level of protein translation but the deacetylation of P53 decreased in type II AEC after hyperoxia exposure. Literatures reported that the desumoylation of SIRT1 could regulate its deacetylase activity. Thus, we presume that some post-translational modifications of SIRT1 regulate its deacetylase activity in type II AEC after hyperoxia exposure, and the sumoylation of SIRT1 may be the key upstream regulator of cell apoptosis induced by P53 in preterm hyperoxia lung injury. In this study, we will prove our hypothesis at molecular, cell, tissue and population level in preterm newborns, hyperoxia exposure newborn rats and type II AEC, by using gene knockout/silence technology, Western blot, confocal laser scanning microscope and liquid chromatography tandem mass spectrometry (LC-MS/MS). We would like to clarify the role of SIRT1 sumoylation in the mechanism of preterm hyperoxia lung injury, and provide new targets for early intervention and treatment of bronchopulmonary dysplasia.