神经肽调控Notch/Delta信号转导通路在发育肺AECⅡ再生修复的相关性研究

The main contents of this research are the changes of Notch/Delta and its downstream signal molecules in the rat lung tissue injury/repair and rat alveolar typeⅡ(AECⅡ)regeneration. We regard the neuropathies which are the regulatory factors to promote reparative and regenerative in AECII as the most important breakthrough point. We choose premature rat lung tissue and the primary cultured AECⅡ as the research object. The original animal model of hyperoxia-induced lung injury in rats and the cell models of AECⅡ regeneration induced by oxidative injuries also will be used. Then the objective of this project intends to explore the following mechanisms of injuries and restoration in AECⅡ:①The regulation and influence of directional differentiation of AECⅡ by the neuropathies in premature rat lung injury.②Whether the neuropathies regulation AECⅡ depends on the Notch/Delta signaling pathways throughout the development process.③What is the relationship of premature rat of Notch/Delta signaling transduction pathway and cytokines expression spectrum and lung regeneration/repair. The innovation of this topic is brought the characteristic concept of fetal wound healing in early gestation with no scar formation to the repair and reconstruction of AECⅡ.We study the relativity between the regeneration and development of lung tissue in the fields of urology, neuroendocrinology and prosthetics. The final purpose is to provide the necessary theoretical basis and potential clinical therapeutic targets for the neuropathies regulate in lung regeneration and development by the process of fetal wound healing with no scar formation.

本项目拟从寻找促进肺泡Ⅱ型上皮细胞(AECⅡ)修复再生的调控因子神经肽类递质为突破口，选择在早产鼠肺组织及其分离的原代AECⅡ细胞为研究对象,肺组织细胞再生修复和Notch/Delta信号途经为研究内容，利用我科原创性细胞氧化性损伤模型。重点解决①神经肽类递质在早产鼠肺损伤时对AECⅡ定向分化的调控及影响，②神经肽类递质调控AECⅡ是否依赖于贯穿发育过程Notch/Delta信号途径③早产鼠肺的Notch/Delta信号转导途径和细胞因子表达谱与肺再生修复的关系。本课题创新之处在于把胎儿无瘢痕愈合这一概念引入AECⅡ的修复重建功能上，从发育学、神经内分泌学和再生修复学的角度研究肺再生与发育肺的相关性，为神经肽调控肺再生修复向无瘢痕愈合发展提供必要的理论依据,为临床可能的治疗提供药物靶点。

本项目拟从寻找促进肺泡II型上皮细胞（AECII）修复再生的调控因子神经肽类递质为突破口，选择不同发育阶段鼠肺组织及其原代AECII细胞为研究对象，肺组织再生修复和Notch/Delta信号途径为研究内容，利用高氧肺损伤动物模型和原创性细胞氧化模型，重点解决：1、神经肽类递质对早产鼠AECII定向分化的调控及影响；2、神经肽类递质调控是否依赖于Notch/Delta信号途径；3、早产鼠肺的Notch/Delta信号途径和细胞因子表达谱与肺再生修复的关系。本项目实施开展的一年以来，我们先后进行了如下工作：1、早产鼠原代肺泡II型上皮细胞的培养、分离及纯化。2、肺泡II型上皮细胞的鉴定、2、神经肽高氧暴露6、12、18、24h后神经肽及其拮抗剂对肺泡II型上皮细胞的影响。对神经肽类递质在早产鼠高氧肺损伤时对AECII定向分化的调控影响以及神经肽类递质调控AECII细胞是否依赖于贯穿发育过程Notch/Delta信号途径方面进行了一系列的探讨，后续蛋白质及核酸水平的实验正在进行中。