MFHAS1通过ERK信号转导通路对脓毒症小鼠T淋巴细胞的作用及机制的研究

脓毒症是临床上常见的危重病之一，病死率较高。恶性纤维性组织细胞瘤扩增顺序1（Malignant Fibrous Histiocytoma amplified sequence 1，MFHAS1）是ROCO蛋白家族的重要一员。我们前期研究发现，其可参与TLR4信号转导通路，对炎症反应起负调控作用。进一步研究发现它还可对脓毒症后期的T淋巴细胞产生增殖作用。但确切作用机制和产生的免疫效应尚未清楚。最近研究表明它可以激活CD34+细胞的Ras\Raf\MEK\ERK信号通路，对细胞的增殖、分化和凋亡起调节作用。本课题通过基因转染、免疫共沉淀、流式细胞仪等分子生物学技术，进一步验证MFHAS1介导ERK信号转导通路的方式和部位，探讨MFHAS1对T淋巴细胞的分化和功能变化的影响，并阐明MFHAS1在脓毒血症后期对适应性免疫系统作用机理，为脓毒血症后期免疫功能调控提供新的思路。

Sepsis is one of the common critical illnesses with high mortality on clinic. Malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) is an important one in ROCO family proteins. Our previous study found, which may be involved in TLR4 signalling pathway, MFHAS1 plays a negative regulatory role in the inflammatory response. In addition, we investigated it can also produce T lymphocytes proliferation during the late sepsis. But the specific mechanisms and immune effect caused by MFHAS1 has not been studied. Recently, people found that it can activate the Ras \ Raf \ MEK \ ERK signalling pathway, which is vital to cell proliferation, differentiation and apoptosis. Hence, we will exam the functional change of T lymphocytes in mice during sepsis through the affection of MFHAS1 acting on ERK signalling pathway by the molecular biology techniques, such as gene transfection, coimmunoprecipitation as well as flow cytometry and explore the mechanism of MFHAS1 to adaptive immune system, which will provide the theoretical support to immunomodulatory treatment of sepsis, especially in T lymphocytes.