肝脏缺血再灌注损伤是导致肝脏移植失败的重要原因，尚无有效治疗手段，因此阐明其发病机理和发现新型药物靶标是亟待解决的关键问题。嗜中性粒细胞是参与肝脏缺血再灌注损伤的关键炎症细胞，其活化机制及在肝脏缺血再灌注损伤中的作用机理尚未完全阐明。MK2是一种丝氨酸/苏氨酸蛋白激酶。前期研究首次发现MK2促进小鼠肝脏缺血再灌注损伤，MK2缺失嗜中性粒细胞生成超氧阴离子明显减少，并首次鉴定MK2直接磷酸化p47phox Ser277位点。本研究拟阐明MK2促进肝脏缺血再灌注损伤的病理机制；探明MK2在嗜中性粒细胞活化中的重要作用；重点探讨MK2通过磷酸化p47phox Ser277 位点调节超氧阴离子产生的分子细节；评价MK2抑制剂III治疗肝脏缺血再灌注损伤的新型药物靶标作用。最终阐明MK2如何通过调控嗜中性粒细胞活化介导肝脏缺血再灌注损伤的分子机制，同时为治疗肝脏移植损伤提供一个潜在的新型药物靶标。

Liver ischemia reperfusion (I/R) injury is an important cause of liver transplantation failure. So far, there are no effective treatments. Therefore, it is vital to understand the fundamental mechanisms and find an effective drug target. Neutrophils are key inflammatory cells associated with liver I/R injury. However the mechanism of neutrophil activation and the role of neutrophils in liver I/R injury haven't yet been fully elucidated. MK2(MAPK-activated protein kinase 2) is a Ser/Thr protein kinase. Based on our novel preliminary data that MK2 is required for liver I/R injury, MK2 deficient neutrophils produced less superoxide and MK2 directly phosphorylates p47phox Ser277, we propose that MK2 modulates liver I/R injury through regulating neutrophil activation. Therefore, the pathological role of MK2 in liver I/R injury and neutrophil activation will be demonstrated. In addition, this studies will also determine the molecular mechanism of MK2 regulating superoxide generation via phosphorylation of p47phox Ser277 and evaluate whether MK2 inhibitor III will be able to alleviate liver I/R injury. Taken together, our findings will not only contribute to the fundamental theory basis of liver I/R injury, but also provide a potential drug target for treating liver transplantation-induced liver injury.