肺泡上皮细胞损伤修复使肺泡化完成是解决早产儿BPD的核心内容。前期研究发现Wnt信号通路在高氧BPD中表达改变导致AEC-Ⅱ增殖转分化异常；并发现，内毒素肺损伤时Wnt5a与lncRNALL18具有一致的时空表达模式。它们的具体关系尚不清楚。本研究拟从模型动物、分子细胞以及基因治疗等水平研究Wnt信号（经典和/或非经典）通路通过lncRNALL18实现与TTF-1转录因子的共活化，调控AEC的增殖转化；预测lncRNALL18与TTF-1DNA或者mRNA的结合位点并验证lncRNALL18靶向激活TTF-1的作用；证实模型动物使用SB转座子、电穿孔技术转lncRNALL18基因方法可以预防或者治疗早产鼠BPD。明确Wnt --lncLL18--TTF-1调控BPD时肺泡化程度，为逐年增多的早产儿BPD的预防和治疗提供新的靶点和思路。

The core content to figure out BPD of premature is to complete alveolization by normalized alveolar epithelial cells repairment after damaging. Previous studies have found that the changes of Wnt signaling pathways lead to abnormal proliferation and transdifferentiation of AEC-Ⅱin the BPD induced by hyperoxia. And it is found that the expression of Wnt5a and lncRNALL18 has the same spatial and temporal expression pattern in the endotoxin induced lung injury. Their specific relationship is unclear. The transcriptional coactive of Wnt（classic and/or non classical） and TTF-1 being mediated by lncRNALL18 would be studied through animal models, molecular cell mechanism and genetic therapy, which regulates AEC proliferation and differentiation. We predict binding sites of lncRNALL18 and TTF-1 DNA or mRNA and testify the role of lncRNALL18 activating TTF-1. We will confirm gene of lncRNALL18 transferred with SB transposon or electroporation technology would prevent or cure BPD of premature rats. Then it may explicit that Wnt --lncLL18--TTF-1 regulates process of alveolization in BPD, provide new targets and ideas for preventing and treating BPD to achieve a better prognosis.