沉默lncRNA-5657对脓毒症大鼠肺损伤的保护作用及机制研究

抑制肺泡巨噬细胞（AM）过度激活是防止脓毒症肺损伤根本措施，研究表明lncRNA参与了单核-巨噬细胞炎症反应的调控，与蛋白相互作用是其发挥生物学功能的重要途径，但lncRNA在大鼠AM炎症反应中的作用未见报道。我们前期采用高通量测序及RT-qPCR验证发现，lncRNA-5657在LPS诱导的大鼠AM炎症反应中表达上调，沉默lncRNA-5657能减少TNFα等炎症因子释放。因此，我们假设lncRNA-5657通过与大鼠AM内某一特异蛋白相互作用，进而促进炎症反应。本项目拟在前期研究基础上，将in vivo-jetPEI介导的lncRNA-5657siRNA经气道滴入大鼠脓毒症肺损伤模型中，探讨其对肺损伤的保护作用；并在大鼠AM内通过RNA-pulldown实验联合质谱分析，鉴定与lncRNA-5657相互作用的蛋白，探讨lncRNA-5657的促炎机制，为治疗脓毒症肺损伤提供新途径。

Inhibition of over-activation of phagocytes in lungs is the main way to protect from septic lung injury. The current studies showed that lncRNA was not only involved in the pathogen-related immune reaction, but also modulated the monocyte-phagocyte inflammatory response through the interaction with protein factors. However, there is no report on the roles of lncRNA in the phagocytes and inflammatory response in the lungs of rats. Our previous study showed that the lncRNA-5657 expression in the alveolar phagocytes of LPS challenged rats was increased measured by HTseq and RT-qPCR, and the LPS induced TNF-α release was decreased by silencing the lncRNA-5677. Thus we hypothesize that the lncRNA-5657 may enhance the inflammatory reaction in the alveolar phagocytes through the interaction with a special protein. This study will explore the protective effects and mechanism on lung injury using vivo-jetPEI mediated lncRNA-5657 siRNA in the rats of the acute lung injury, and detect the special protein interacting with lncRNA-5657 by in vitro RNA-pulldown and MS analysis. This study will provide a new way to treat acute lung injury through the mechanism of lncRNA-5657.