糖尿病（dibetes mellitus，DM）创面难愈是临床棘手问题，研究表明高糖诱导核因子FOXO1乙酰化将其促创面愈合逆转成延迟创面愈合是导致创面难愈的关键，我们已证实Ski具有促DM创面愈合的作用，但机制还不清楚，文献表明Ski可介导HDAC1去乙酰化调节与其结合的核因子，预实验证实Ski与FOXO1的结合可降低FOXO1的乙酰化水平，因而推测Ski结合FOXO1并募集HDAC1去乙酰化FOXO1可能是Ski促DM创面愈合的重要机制。本研究拟在高糖诱导的细胞损伤模型中，首先采用IP验证Ski、FOXO1和HDAC1的相互作用，进而采用WB、TUNEL、BrdU等法检测Ski作用后FOXO1的乙酰化水平及细胞凋亡、增殖及胞内ROS生成情况，最后采用HDAC1激动剂或siRNA证实Ski是通过HDAC1去乙酰化FOXO1来促进DM创面愈合的，为将Ski作为促愈药物的研发提供理论依据。

Diabetes wound healing is a difficult problem in clinical. The research showed that the cell proliferation will reverse the apoptosis which induced by FOXO1 under hyperglycemia condition is the key to dalay wound healing. We confirmed that Ski can promote wound healing of DM, but its mechanism is not clear. The literature indicate Ski, as a corepressor, can recruit HDAC1 and mediate the deacetylation effect of its nuclear factor. The pre-experimen confirmed the combination of Ski and FOXO1 can significantly reduce the acetylation level of FOXO1. Therefore, it is speculated that Ski combined with FOXO1 and raised deacetylation of FOXO1 and then reverse promoting the apoptosis of cells to inducing the proliferation may be an important mechanism of Ski promoting DM wound healing. In this study, in hyperglycemia-induced-cell injury model, we comfirm the interaction of Ski、HDAC1 and FOXO1 using IP firstly, and then detect.level of FOXO1 acetylation and the ability of cell apoptosis and proliferation by WB, Tunel, BrdU and other methods. Finally, we use HDAC1 inhibitors or siRNA to explore the pro-healing of Ski was achieved by regulating the acetylation level of FOXO1, This study will provide a solid foundation for development of the new pro-healing drugs based on Ski