脓毒血症（sepsis）是临床上急性感染性病人主要的并发症，单核巨噬细胞产生的TNF-a的增加在sepsis发生发展过程中发挥重要的作用,降低TNF-a水平是目前一个主要的研究方向。我们以往的研究发现，用THP-1细胞模拟sepsis体外模型时，SIRT1对TNF-a的转录具有抑制作用，但是在sepsis发生发展过程中，SIRT1的抑制作用是何时开始发挥的，以及用SIRT1激活剂是否可以在此过程中起到抑制TNF-a转录的作用呢，本课题拟通过观察SIRT1激活剂对THP-1细胞中TNF-a转录的影响，探讨SIRT1激活剂对预防和治疗sepsis的作用；并通过应用染色体免疫沉淀等技术观察SIRT1激活剂对TNF-a启动子区表观遗传修饰的影响，在细胞和分子水平证实我们的假设，进而为临床预防和治疗sepsis等炎症性疾病提供新的思路奠定基础.

Sepsis is the main complication of acute infection in clinic. TNF-a produced by monocyte macrophage has a major role in the development of sepsis and reducing TNF-a is an importment way of treatment at present.Our previous research found that SIRT1 could reduce TNF-a transcription in THP-1 cells of sepsis model. But when and how SIRT1 inhibite TNF-a transcription are not very clear. It is not known whether SIRT1 activator could inhibite TNF-a transcription in the development of sepsis. This research would concentrate on sepsis prevention and treatment by SIRT1 activator through studying the TNF-a transcription by SIRT1 activator in THP-1 cells; And confirming our hypothesis in celluar and molecular level by studying the epigenetic modification of TNF-a promoter by SIRT1 activator through chromatin immunoprecipitation (ChIP) method. We hope to provide new way of prevention and treatment in curing such inflammation diseases as sepsis in clinic.