柴油机尾气（DEE）是一种普遍的职业危害因素，长期暴露会引起小气道病变，而小气道病变的发生往往与支气管上皮细胞（HBE）损伤后修复异常有关，但目前关于DEE暴露对HBE损伤修复的影响及机制尚不明确。本项目前期研究发现，长期DEE暴露可降低受损HBE修复的效应指标，并抑制ΔNp63表达，提示ΔNp63在DEE干扰HBE损伤修复中扮演重要角色。因此我们提出以下科学假说：长期DEE暴露通过调控ΔNp63干扰HBE损伤修复。本项目拟首先明确长期DEE暴露导致HBE损伤修复异常与小气道病变的关联；考虑到HBE受损后修复过程的复杂性，首次系统阐述长期DEE暴露干扰HBE损伤修复的关键阶段；最后通过建立ΔNp63过表达体系，探究ΔNp63在DEE干扰HBE损伤修复中的角色和分子机制。项目实施将丰富对职业DEE暴露致小气道病变机制的认识，为精准预防DEE引起的小气道病变提供理论依据。

Diesel engine exhaust (DEE) is an occupational hazard factor, which can induce small airway damage. Small airway damage is directly related to abnormal repair of bronchial epithelial (HBE). However, the effect and mechnasim of DEE on HBE damage repair is unclear. In addition, we have found that DEE exposure down-regulated the HBE repair biomarker and ΔNp63, which is responsible for HBE repair interfered by DEE. On the basis, we hypothesize that long term DEE exposure induce abnormal HBE damage repair by the regulation of ΔNp63. In this project, we first explore the relationship between HBE abnormal repair induced by DEE and small airway diseases. Next, considering the complex of HBE repair process, the role of DEE on different period of HBE repair is evaluated. Finally, the role and mechanism of ΔNp63 in DEE-induced abnormal repair of HBE is explained by up-regulated ΔNp63 expression. This project will be helpful to better understand the toxicity of DEE and conduction of health monitoring.