甲醛暴露与IL-13基因多态性的交互作用对支气管平滑肌细胞功能的影响

Asthma is the most common chronic respiratory disease in children, characterized by airway inflammation and bronchial smooth muscle contraction. It has been known that asthma may be as a result of the combined effects of genetic and environmental factors. Our previous studies have revealed that IL-13 gene polymorphism may be related to the development of asthma in Chinese Han children and its recombinant protein plasmid, IL-13 R110Q, had a significantly positive effects on the asthma-associated functions of bronchial smooth muscle cells in vitro. Our results also showed that indoor formaldehyde exposure may be one of the most important environmental factors for child asthma. However, no studies could be available to indicate the possible synergistic effects of formaldehyde exposure and IL-13 gene polymorphism. Our study, which will be underwent in vitro and in animal models, is aimed to investigate the interaction between formaldehyde exposure and IL-13 gene polymorphism on the functions of bronchial smooth muscle cells and the pathological changes of airways, so as to further reveal the complex pathogenesis of child asthma.

哮喘是儿童时期最常见的慢性呼吸系统疾病，以气道慢性炎症、支气管平滑肌收缩、气道狭窄为主要病理变化。现已明确，哮喘是由遗传和环境因素共同作用的结果。我们前期研究发现，IL-13基因多态性位点A2044G与中国儿童哮喘的发生密切相关，由其构建的重组蛋白质粒IL-13 R110Q在体外致哮喘作用显著增强；而甲醛暴露则是儿童哮喘发生的一项重要环境因素。然而，IL-13基因多态性与甲醛暴露之间是否存在协同致病作用，目前尚无研究证实。本项目拟从体外和动物模型两个层面，深入研究甲醛暴露和IL-13基因多态性的交互作用对于支气管平滑肌细胞功能和气道病理的影响，从而进一步揭示儿童哮喘复杂性状的发病机制。

支气管哮喘(简称哮喘)是儿童时期最常见的慢性呼吸道疾病。近年来，我国儿童哮喘的患病率呈现显著上升趋势。流行病学研究提示室内甲醛暴露可能与儿童哮喘发病增加有关。但是，对于甲醛暴露是否会诱导或加重哮喘，目前尚无确切的研究。本研究采用Balb/c和C57bl/6小鼠构建非致敏和OVA致敏小鼠模型，分别予0、0.5mg/m3、3.0 mg/m3甲醛暴露，每天6h, 连续暴露25天。末次暴露24小时后，测定肺泡灌洗液中细胞因子水平以及白细胞总数和细胞分类计数；测定血清中OVA特异性免疫球蛋白浓度；测定气道的吸气阻力和呼气阻力。同时，本研究以气道平滑肌细胞为切入点，通过高通量技术筛选甲醛诱导气道平滑肌细胞差异表达的mRNAs和lncRNAs，寻找与甲醛诱发哮喘相关的mRNAs和lncRNAs并探讨其功能与机制。结果：(1)甲醛暴露可诱导非致敏的Balb/c和C57bl/6小鼠发生气道炎症和气道高反应性。OVA致敏的Balb/c和C57bl/6小鼠经过不同浓度的甲醛染毒后，表现出不同的免疫增强或抑制反应; (2)Balb/c小鼠和C57bl/6小鼠在甲醛易感性及其免疫反应方面存在明显差异，与C57bl/6小鼠相比，Balb/c小鼠对甲醛诱导的气道炎症和气道高反应性更敏感; (3)我们通过芯片筛选出的差异mRNAs和lncRNAs，与哮喘生物学特征密切相关。结论：甲醛暴露对Balb/c和C57bl/6小鼠在气道炎症和气道高反应方面的影响不同，与遗传背景有关。甲醛可能通过调节免疫相关的mRNAs和lncRNAs的表达，诱导气道炎症和气道高反应性的发生。