小分子肽ABPDP1在支气管肺发育不良防治中的作用机制研究

Bronchopulmonary dysplasia (BPD) is a common complication in premature infants, without effective interventions. ABPDP1 is a novel bioactive peptide identified from human breast milk. Previously, we found it could promote the proliferation and differentiation of AT II cells. It indicated that ABPDP1 might be used in BPD treatment. Further study revealed its function was related to Notch2 activation. In addition, it is well established that Notch2 signaling is critical for AT II cells proliferation and differentiation. We intent to verify its protective functions in BPD prevention in vivo and vitro. Rescue experiments and pull-down assay will be carried out to explore the molecular mechanisms of ABPDP1 and to screen its direct target. Our research might provide a novel approach in BPD treatment in future.

支气管肺发育不良（BPD）是早产儿最常见的并发症之一，尚缺乏有效的治疗手段。ABPDP1是我们从母乳中发现的一条新型小分子肽，未见相关功能报道。前期发现，ABPDP1具有促II型肺泡上皮（ATII）细胞增殖、分化的功能，展示出可能作为BPD防治手段的潜质。机制研究揭示，ABPDP1可激活Notch2信号通路，已报道Notch2信号通路可调控ATII细胞的增殖与分化。本研究拟在前期基础上，通过体外和体内实验论证ABPDP1通过促进ATII细胞增殖和分化用于BPD防治的可能性；以Notch2信号通路为机制线索，通过挽救实验策略深入论证其分子机制，并运用Pull-down实验寻找其直接结合靶标。研究具有源头创新性，如获成功有望为BPD提供潜在的防治手段。

支气管肺发育不良（BPD）是早产儿最常见的并发症之一，缺乏有效的治疗手段。循证医学和临床实践证实，母乳喂养可有效降低BPD的发生率改善其预后。在本课题实施过程中，我们对母乳中含有的各类小分子活性物质展开探索，揭示了外泌体、非编码RNA、多肽和脂质等均是介导母乳喂养健康效应的重要活性成分。探索发现，富集于母乳中的小分子多肽ABPDP1具有减轻高氧诱导II型肺泡上皮（ATII）细胞的损伤的功能。进一步的机制研究发现，ABPDP1具备促进Notch2信号通路改善ATII细胞增殖、分化的生物功能，有望成为BPD防治手段的潜在干预手段。