急性肺损伤(ALI)致死率高，故阐明ALI致病机理是提高抢救成功率的关键。百草枯(PQ)诱导小鼠急性肺损伤是典型急性氧化应激损伤模型。前期采用新型全转录本基因芯片检测了PQ致小鼠肺损伤全基因转录表达谱,经生物信息学分析确立：Nlrc5是PQ致肺损伤差异基因共表达细胞内信号传递网络最重要的核心调控基因；Western Blot证实小鼠6h肺组织Nlrc5增高，24h则显著降低；茶多酚(EGCG)可显著减低PQ中毒小鼠的死亡率。体外研究证实Nlrc5能同时显著抑制NF-kB和I型IFN通路。故认为：Nlrc5分子下调致NF-kB和I型IFN通路活化是氧化应激肺损伤的关键机制。为此，采用反相蛋白微阵列技术和PQ中毒患者样本，系统研究Nlrc5在氧化应激肺损伤中的调控机制和EGCG的干预作用及其与NF-kB的关系。为探索基于特异干预Nlrc5 分子和茶多酚联合治疗氧化应激肺损伤新方案提供实验依据。

Respiratory failure is the biggest cause of highest mortality rate of Paraquat (PQ) poisoning. So how to clarify the main pathogenic mechanism of ALI is the key to improve the success rate of rescue. Whole profiling of gene expression and transcription of lung tissue in PQ poisoning mice was detected previously using a newly whole-genome transcription of gene chips, and then the profiling of differential gene expression was determined. Bioinformatics analysis established: ① Nlrc5 is the most important core regulatory gene in intracellular signaling network of differential gene-co-expressed cells in lung injury of PQ poisoning mice. ②Nlrc5 significantly increased after 6h of lung tissue in PQ poisoning mice and largely reduced after 24h using quantitative PCR and Western Blot. In vitro studies confirmed that Nlrc5 was able to significantly inhibit both NF-kB and type I IFN pathway. Therefore, we believe that sustained NF-kB and type I IFN pathway activation induced by downregulation of Nlrc5 is a key mechanism to PQ-induced pulmonary injury. To validate our conclusion, combining the data from bioinformatics analysis and reverse phase protein microarray, we will systematically study the role of the core regulatory gene, Nlrc5, in the PQ induced lung injury, and explore its critical signaling pathways. Not only will this study deepen the understanding of gene function in Nlrc5, but it provides new clues for the next specific interventions.