为研究高氧致慢性肺疾病（CLD）早产鼠Wnt信号通路对Ⅱ型肺泡上皮细胞（AEC-Ⅱ）增殖及其向Ⅰ型肺泡上皮细胞（AEC-Ⅰ）转化的调控机制。采用已建立的高氧诱导早产鼠CLD模型及体外培养AEC-Ⅱ及其转化的AEC-Ⅰ，应用PCR、蛋白印迹、细胞内转染、免疫共沉淀等多种分子、细胞生物学技术，研究：1）不同种类Wnt启动的（Wnt/β-catenin、Wnt/PCP、Wnt/Ca2+）三条通路中主要基因和蛋白在早产鼠正常肺发育及CLD发生中的肺组织以及AEC-Ⅱ中表达规律；2）改变Wnt启动的三条途径活性对CLD早产鼠AEC-Ⅱ增殖转化的影响。试图证实：Wnt信号通路异常激活、抑制、它们之间平衡关系破坏而导致AEC-Ⅱ的细胞周期调控紊乱以及AEC-Ⅱ分化为AEC-Ⅰ能力降低是高氧CLD肺泡上皮细胞损伤后修复障碍和肺泡化障碍的重要机制之一。为早期有效防治早产儿CLD奠定理论与实验基础。

To study Wnt signal transduction in chronic lung disease induced by hyperoxia in premature rats and its regulation mechanism of proliferation of typeⅡ alveolar (epithelial) cells（AEC-Ⅱ）and its differentiation to type I alveolar (epithelial) cells (AEC-I ). We adopt the ready-made CLD models induced by hyperoxia in premature rats. Meanwhile, we culture original AEC-Ⅱof these models and AEC-I differentiated from AEC-Ⅱ.Using PCR,Western-Blotting,transfection in cell, co-immunoprecipitation and other molecular biology or cytobiology technologies to study:1) Different kind of Wnts switch on three（Wnt/β-catenin、Wnt/PCP、Wnt/Ca2+） different signal transductions, to explore the expressing patterns of their main genes and proteins in lung tissue of normal and CLD premature rats and AEC-Ⅱ. 2)Changes of AEC-Ⅱ ability to proliferation and differentiation to AEC-Ⅰby changing activity of Wnts switching on different signal transductions. Trying to confirm: Abnormality of Wnt signal transductions in activition, inhibition or disturbance of their balance would result in disorder of generation cycle of AEC-Ⅱand decreased ability to differentiation to AEC-Ⅰ, which was one of the most important mechanisms of alveolar epithelial cell dysreepithlialization in chronic lung disease induced by hyperoxia.It should be theoretical and experimental foundation to prevent and treat CLD in newborns in early time.