淋巴细胞过度凋亡对脓毒症患者预后可能具有决定性作用，但其凋亡机制不清。研究发现，TCTP结合Mcl-1可减少Mule介导的Mcl-1泛素化降解。而作为Bcl-2家族成员之一，Mcl-1表达可抑制凋亡。但关于TCTP调节Mcl-1泛素化降解是否参与脓毒症患者淋巴细胞凋亡，未见报道。本课题通过TCTP 、Mcl-1 基因转染、Mule siRNA等干预脓毒症患者血清诱导的HUT-78细胞凋亡，并用Real-time PCR、免疫印迹法、免疫共沉淀、共聚集显微镜等技术观察淋巴细胞凋亡、TCTP、Mcl-1、Mule mRNA及蛋白表达、结合及其Mcl-1泛素化降解水平，以深入研究TCTP调节Mule介导的Mcl-1泛素化通路在脓毒症患者淋巴细胞过度凋亡中的关键作用。

Lymphocyte apoptosis has been recognized as an important step in the pathogenesis of experimental sepsis,by inducing a state of 'immune paralysis' that renders the host vulnerable to invading pathogens.Excessive lymphocyte apoptosis potentially play a crucial role in progonsis of patients with severe sepsis.Mcl-1,an anti-apoptotic Bcl-2 family member, appears to function at an apical step in many regulatory programs that control cell survival and death.Overexpression of Mcl-1 delays cells from undergoing apoptosis.The extremely labile nature of the Mcl-1 protein itself and the fact that the Mcl-1 level is a critical determinant in various cell survival pathways suggest that cellular processes that regulate Mcl-1 stability are as important as those that regulate Mcl-1 synthesis.TCTP bound to Mcl-1 and modulated the stability and antiapoptotic activity of Mcl-1 via interfering with Mcl-1's ubiquitin-dependent proteasome degradation,which was mediated by Mule,Mcl-1 ubiquitin ligase E3.However, whether Mcl-1 ubiquitination modulated by TCTP via Mule is involved in T lymphocyte apoptosis in sepsis patientsis is elusive. We measure apoptosis in circulating lymphocytes from patients with severe sepsis, and treate HUT-78, pretransfected with TCTP, Mcl-1 cDNA or Mule siRNA,with serum from patients with sepsis, then, measure lymphocyte apoptosis, the mRNA and protein level of TCTP,Mcl-1 and Mule,the ubiquitin-dependent degradation of Mcl-1,aim to learn the effect of Mcl-1 ubiquitination modulated by TCTP via Mule on T lymphocyte apoptosis in sepsis patients.