PM2.5通过lncRNA调控NF-κB促进气道炎症的机制研究

随着大气污染的日益严重和慢性阻塞性肺疾病（慢阻肺）患病率的上升，大气细颗粒物（PM2.5）在慢阻肺发病中的作用日益受到关注，但其机制尚不甚明了。我们前期研究发现，置大鼠于模拟室内空气污染环境时，炎症因子表达水平上升伴有肺内长链非编码RNA（lncRNA）表达谱变化；进一步研究发现，慢阻肺患者肺组织内也呈现炎性因子表达水平上升并伴有lncRNA表达谱变化。核转录因子-κB（NF-κB）是调控炎症的关键因子，在PM2.5诱导的炎症反应中起到核心的调控作用。但PM2.5是否和如何通过lncRNA作用影响气道炎症效应的机制并不清楚。本课题拟从慢阻肺患者肺组织和PM2.5刺激气道上皮细胞中筛选出两条异常高表达并可能影响炎性因子和NF-κB通路的lncRNA（RP11-86H7.1和ENST325042）基础上，从分子水平探讨其在PM2.5致慢阻肺气道炎症效应的调控机制，以期为慢阻肺治疗提供新的靶点。

A growing number of studies have shown that the environmental stimuli, such as biofuel exposure and air pollution play an important role in the development of COPD. These harmful particles or gases can cause increased airway chronic inflammation and an oxidation-antioxidation imbalance, leading to abnormal airway and/or alveoli, aggravating respiratory symptoms and limiting airflow in patients with COPD. We recently found that exposure to high particulate matter (PM) concentrations, especially PM2.5, was associated with an increased prevalence of COPD and decreased respiratory function. With the rapid urbanization and increasing industrialization in China, PM2.5 from traffic-related air pollution formed by motor vehicle exhaust has become a major source of air pollutant emissions. However, it is unclear how PM2.5 leads to COPD pathogenesis. It has recently been discovered that long noncoding RNAs (lncRNAs) play a role in the occurrence and development of many respiratory diseases, especially lung cancer. lncRNAs are a class of RNAs that are more than 200 nucleotides in length, which have important functions in various aspects of cell biology and life processes. Our recent study found that inflammation cell infiltration and increased expression of inflammtory factors in PM2.5 induced rats model, also the lncRNA expression profile was changed. Our further findings showed that the increased expression of inflammtory factors accompanied by the variational lncRNA expresssion profile in lung tissue samples from COPD paitents. Nuclear transcription factor - B (NF-κB) is a key factor regulating inflammation and it plays a central role in PM2.5 - induced inflammation.However, the mechanism of whether and how PM2.5 affects airway inflammation through lncRNA is not clear.In the pre-experiment we had screened two lncRNAs (RP11-86H7.1 and ENST325042) from COPD patients and cell model of PM2.5 stimulation respectively, which could regulate the inflammtory factors and the function of NF-κB pathway. We will research the molecular mechansim of lncRNA in PM2.5 induced airway inflammatory effect. This project will elucidate the key role of lncRNAs in the pathological process of airway inflammation caused by PM2.5 and to analyze their relationships with the occurrence and development of COPD.