细胞外基质SPARC在败血症炎症反应中的作用及机制研究

Extracellular matrix, as a key component of inflammatory microenvironment, regulates the storage of inflammatory cytokines and infiltration of inflammatory cells. SPARC was highly expressed in stromal cells, and which upregulated during tissue injury and infection. However, the role of SPARC in septic inflammation is still unclear. It was reported that the immune response was deregulated and inflammatory cell infiltration was decreased in SPARC-deficient mice. We found that serum SPARC level was markedly increased in patients with sepsis; the mortality of SPARC-deficient endotoxemic mice was drastically reduced, and IL-1β expression decreased. Taken together, these data above suggest that SPARC regulates the processes of septic inflammation. Thus, in this study, we will use SPARC-deficient mice an an animal model : 1. to define the role of SPARC in septic inflammation; 2. to explore the signal pathway of SPARC regulating septic inflammation; 3. to analyze the correlation of serum SPARC level and inflammatory cytokines in patients with sepsis. This study will provide a new theoretical basis for prevention and treatment of sepsis.

细胞外基质作为炎症微环境的重要组分，参与调节炎性因子的储存和炎症细胞的浸润。SPARC高表达于基质细胞，在组织损伤和感染时表达上调，但是SPARC在败血症炎症反应中的作用尚不清楚。已知SPARC缺失小鼠的免疫反应性降低，炎症细胞浸润减少。在预实验中，我们发现败血症患者血清SPARC水平明显升高；SPARC缺失型内毒素血症小鼠的死亡率明显降低，炎性因子IL-1β表达减少，提示SPARC参与调节败血症炎症反应的进程。本课题拟采用SPARC缺失型小鼠作为动物模型：1.明确SPARC在败血症炎症反应中的作用；2.探讨SPARC影响败血症炎症反应的信号途径；3.分析败血症患者血清SPARC水平与炎性因子的相关性。此研究将为败血症的防治提供新的理论依据。