RSV是造成5岁以下儿童严重呼吸系统疾病最常见的病毒，婴幼儿RSV感染对哮喘发生发展起重要作用。目前药物治疗在病毒诱发哮喘方面存在困难并出现耐药。我们前期研究发现哮喘易感基因ORMDL3在RSV诱发哮喘动物模型肺组织中表达增高，可能是RSV与哮喘关系间的桥梁。RSV可激活NLRP3炎症体导致炎症扩散，而ORMDL3过表达质粒转染支气管上皮细胞后NLRP3表达也增多。ORMDL3基因启动子上组蛋白乙酰化酶p300与之结合并调控表达。我们推测RSV感染诱发哮喘中，通过组蛋白乙酰化影响ORMDL3表达从而激活NLRP3炎症体过度释放。本课题拟通过体内外实验证明ORMDL3对NLRP3炎症体激活的影响，并在RSV诱发哮喘小鼠模型检测组蛋白乙酰化、ORMDL3与NLRP3炎症体间关系，予p300抑制剂C646可抑制其表达缓解哮喘病理改变。本研究从RSV诱发哮喘的发病机制找出新干预环节和治疗靶点。

RSV is the most common virus causing severe respiratory disease in children under 5 years. RSV infection in early life stage plays an important role in the development of asthma. Current therapy control the episode of asthma induced by virus face to challenge because β2 receptor agonist insensitive or hormone resistance. It is urgent to explore the mechanism of RSV induced asthma to find a new treatment breakthroughs. Our previous study found that the expression of asthma susceptibility gene ORMDL3 increased in the lung tissue of RSV induced asthma animal model, which indicated that ORMDL3 maybe the link between RSV and asthma. RSV infection could activate NLRP3 inflammasomes and cause inflammation cascade effect, and the expression of NLRP3 increased after transfection of ORMDL3 overexpression plasmid to bronchial epithelial cells. The histone acetylase p300 on the promoter of the ORMDL3 gene is the key of its regulatory mechanism. We speculate that histone acetylation regulate the expression of ORMDL3 activates the over release of NLRP3 inflammasome in RSV induced asthma. The aim of this study is to prove the effect of ORMDL3 on the activation of NLRP3 inflammasome through in vivo and in vitro experiments, and to detect the relationship between histone acetylation, ORMDL3 and NLRP3 inflammasome in RSV induced asthma mouse model. The p300 inhibitor C646 can inhibit the expression of ORMDL3 and NLRP3 inflammasome and relieve the pathological changes of asthma. In this study, we will find new intervention and therapeutic targets from the pathogenesis of RSV induced asthma.