NF-κB调控肺间充质干细胞在支气管肺发育不良致病机制中的作用

Bronchopulmonary dysplasia (BPD) impacts seriously on the survival and prognosis of the premature children. Its pathogenesis remains unclear. Some previous studies demonstrated that the myofibroblastic differentiation of the resident lung mesenchymal stem cells (L-MSCs) promotes the development of BPD in the preterm children under exposing to the external pathogenic stimuli. The inflammatory stimulation is the most important external pathogenic factor contributing to the development of BPD. The NF-κB signaling pathway plays a key role of inflammation responses, which is closely related to inflammatory lung injury, and regulates some important biological properties of MSCs such as proliferation, differentiation, migration, and immune regulation. Based on the above, we could make a hypothesis that the biological behavior abnormalities of the resident L-MSCs induced by inflammatory stimuli via the NF-κB signaling pathway results in the development of BPD. But there were none such research reports so far, therefore that is the scientific topic discussed in our research. In this study, we intend to assess the role of NF-κB signaling pathway in L-MSCs systematically by observing that the NF-κB signaling pathway regulates the biological behaviors of the resident L-MSCs such as proliferation, migration, differentiation and myofibroblast differentiation by establishing a BPD animal model with Kunming mouse and isolating the resident L-MSCs from Kunming mice also to explore the intervention effect of L-MSCs on the BPD mice model for clarifying the relationship of the stimulated resident L-MSCs with the development of BPD. As a result, the new clues or experimental evidences could be presented associated with the pathogenesis of BPD.

支气管肺发育不良（BPD）是影响早产儿生存及预后的重要因素。研究提示早产儿内源性肺间充质干细胞（L-MSCs）在炎症等外部致病因子刺激下向肌成纤维细胞分化可促进BPD的发生。NF-κB是炎症调控的核心信号通路，与炎症性肺损伤关系密切；参与调节多种MSCs生物学行为。据此可推测炎症刺激可能通过NF-κB信号通路引起内源性L-MSCs的生物学行为异常促使了BPD的发生。但目前尚未见此类研究报道。而这正是本研究拟解决的科学问题。本研究拟通过建立KM小鼠BPD模型并分离L-MSCs，从增殖、迁移、分化等MSCs生物学行为以及成肌纤维细胞分化方面探讨NF-κB对L-MSCs的影响。系统性评估NF-κB对L-MSCs的生物学行为的调控作用。并通过观察L-MSCs对BPD小鼠的干预作用，最终阐明L-MSCs在炎症刺激下的生物学行为改变与BPD的关系。为研究BPD发病机制提供新的线索及实验证据。