系统性红斑狼疮（SLE）是自身免疫性疾病中的常见病和难治病，其发病机制至今未明。DNA低甲基化状态是SLE表观遗传学的重要病理特征。GSK3β是维持DNA甲基化的重要激酶。多胺是广泛存在于细胞核内的小分子，影响DNA多种功能。研究发现多胺可以促进AKT/GSK3β细胞信号通路磷酸化而减少GSK3β含量。同时，多胺类似物可以诱发药物性狼疮（DIL）。因此我们推测多胺可以通过AKT／GSK3β通路抑制DNA甲基化而参与SLE发病。本项目将利用高效液相色谱、免疫磁珠分选和蛋白质印迹技术等检测多胺对SLE DNA甲基化的影响，特别是AKT／GSK3β信号通路在其中的作用。我们还将检测饮食添加多胺对狼疮小鼠动物模型的影响。本课题的研究结果将有助于明确多胺对SLE DNA低甲基化状态及其他细胞功能的影响和调控机制，为SLE发病学说提出新的理论基础和实验依据。

Systemic Lupus Erythematosus (SLE) is a common and refractory disease in autoimmune diseases and its pathogenesis is still unknown. The hypomethylation of DNA is one of the most important pathological characteristics of SLE epigenetic. GSK3βis a critical kinase to maintain DNA methylation. Polyamines are small biogenic amines in eukaryotic nucleus and prokaryotic cells. They bind to DNA and widely involved in DNA functions. Researchers found polyamines could activate AKT/GSK3βpathway to decrease GSK3β. Moreover, the analogue of polyamines could induce drug induced lupus (DIL). Therefore we assume that polyamines can inhibit SLE DNA methylation by AKT/GSK3βpathway. We will use HPLC, MACS and western blot to detect the effects of polyamines on DNA methylation, especially for the function of AKT/GSK3βpathway. We will also increase the intake of polyamines in lupus animal’s diet, to observe the following results. This study will help to reveal the potential mechanism of polyamines on SLE DNA methylation and to provide new theoretical basis and experimental data for SLE pathogenesis.