TLR4/MD-2高表达在输血相关急性肺损伤中的作用及机制研究

输血相关急性肺损伤（TRALI）是输血相关死亡首因，其机制尚不明确。前期研究我们证实TLR4/MD-2介导的炎症反应与肝移植急性肺损伤（ALI）密切相关；在TRALI细胞模型的预实验中，我们已初步证实TLR4/MD-2表达与相关炎性因子水平呈正相关。鉴于TRALI属ALI的一种，我们提出“TLR4/MD-2表达上调导致炎症失控与TRALI有关”假设。本项目拟建立TRALI细胞和动物模型，观察TLR4/MD-2表达、NF-κB、IL-2等因子的变化；再通过SiRNA特异性沉默MD-2及使用阻断剂等阻断TLR4/MD-2信号传导，明确是否能降低相关炎性因子水平并减轻肺损伤程度，从而证明TLR4/MD-2是介导TRALI的关键调控通路。本项目可望阐明TLR4/MD-2高表达介导炎症反应在输血相关急性肺损伤中的作用及其主要信号通路，为确立TLR4/MD-2作为TRALI治疗的靶点提供科学依据。

Transfusion-related acute lung injury (TRALI) is the leading cause of blood transfusion related death.Its pathogenesis is not clear. In our previous studies we confirmed that the inflammatory response mediated by TLR4/MD-2 is closely related to acute lung injury (ALI) in liver transplantation. In the preliminary experiment of TRALI cell model, it has been preliminarily confirmed that the expression of TLR4/MD-2 is positively correlated with the inflammatory factors.In view of TRALI is a type of ALI we put forward the hypothesis that “upregulation of TLR4/MD-2 plays a critical role in TRALI resulted from over inflammation”. In this study TRALI models of cells and animals will be established.We will observe the expression of TLR4/MD-2,IL-2,NF-κB.We will also use RNA interference and blocking the TLR4/MD-2 to observe the relevant indexes changes. This project is expected to explore the role of TLR4/MD-2 and its main signaling pathway.It can provide a scientific basis of TLR4 / MD-2 as a target for TRALI therapy.