急性肺损伤微环境调控肺泡上皮细胞修复作用与机制研究

ALI后肺泡组织的修复与再生决定着ALI/ARDS患者的预后。我们前期研究发现：①一定程度ALI后肺泡上皮具有较强的自我修复能力；②ALI肺组织匀浆液和肺泡灌洗液均能促进肺泡上皮细胞修复，以匀浆液作用更明显；③ALI早期组织匀浆液可刺激AEC2细胞发生可塑性变化；④ALI后肺组织内多种生长因子呈不同的变化规律。然而，关于ALI微环境变化如何激活并调控肺泡上皮的修复，目前尚不清楚。本项目以ALI微环境为调控因素，系统研究AEC2和AEC1修复作用的启动与调控，探讨ALI微环境内化学与物理因素的不同调控作用，利用蛋白质组方法，系统筛选ALI微环境中调控肺泡上皮细胞的关键因子，利用信号转导技术，系统研究ALI微环境调控肺泡上皮修复作用的分子机制。旨在揭示ALI后肺泡自我修复与再生的内源性调控机制与关键调控因素，为解决ALI/ARDS的治疗难题提供理论基础与思路

Repair and regeneration of alveolar tissue determines the prognosis of patients with ALI/ARDS. To enhance the repair ability of alveolar tissue is the most effective approach to solve the problem of ALI/ARDS treatment. Previously, we have found that: ① Alveolar epithelium has a strong self-repair ability after certain extent of ALI; ②Both lung tissue homogenate and bronchoalveolar lavage fluid from ALI lung tissues can promote the repair of alveolar epithelial cells, with homogenates showing more significant effects; ③In early-stage ALI homogenate AEC2 cells showed a certain degree of plasticity; ④After ALI, a variety of growth factors in lung tissue showed different patterns of changes. However, it remains unclear how the change of ALI microenvironment activates and regulates repair ability of alveolar epithelial cells. The current project aims to systematically study the Initiators and regulators of repair ability of AEC1 and AEC2 after ALI, to investigate the different regulation mechanisms of chemical microenvironments (lung homogenates) and physical microenvironments (bio-electric fields) on AEC1 and AEC2 behaviors, to systematically screen key factors regulating alveolar epithelial cell behaviors using a proteomics approach, and to study the molecular mechanisms for regulation of repair ability of alveolar epithelial cells by ALI microenvironments using signal transduction of protein chip technology. In summary, the current project aims to reveal both endogenous regulation mechanisms and key regulatory factors for alveolar self repair and regeneration after ALI, and to provide theoretical basis for finding measures to repair pulmonary tissue in patients with ALI/ARDS.