GSTM1基因缺失对雾霾所致急性呼吸道炎症的影响及其机制

以PM2.5浓度超标为特征的雾霾污染正在我国大面积频发，导致居民急性呼吸系统疾病发病率上升。研究雾霾致病机制、识别雾霾危害易感人群具有重要现实意义。GSTM1是肺脏中一个主要抗氧化酶，约53%中国人缺少GSTM1基因。课题组观察到GSTM1基因缺失可加重空气污染物对呼吸道上皮细胞的炎性作用，推测GSTM1基因缺失可能是雾霾危害的易感因素。为此，将利用人群定组研究和人呼吸道原代上皮细胞体外模型，揭示GSTM1基因缺失是否能加重雾霾对呼吸道的急性炎性作用及其机制。定组研究是在不同雾霾天气条件下，利用诱导痰技术分别对GSTM1阳性和阴性健康志愿者进行6次呼吸道急性炎性反应检测，再利用统计学模型分析GSTM1基因缺失是否可加重雾霾所致的呼吸道炎症。体外研究除了验证GSTM1基因缺失是否能增强雾霾的炎性作用外，重点阐明GSTM1基因缺失是通过影响哪些细胞内信号传导通路来增强雾霾的炎性作用。

Haze air pollution, characterized by above-standard PM2.5 levels, takes place frequently in a large area of China, resulting in higher incidence of acute respiratory diseases. Thus, elucidation of the mechanisms for haze-related lung diseases and identification of susceptible population to haze toxicity is of practical significance. The glutathione S-transferase M1 (GSTM1) is a major antioxidant enzyme in human lung and about 53% of Chinese population presents GSTM1 null genotype. We have recently shown that the bronchial epithelial cells with GSTM1 null genotype responded more severely to air pollutant treatment than those with GSTM1 positive genotype. It is assumed that GSTM1 deficiency may act as a susceptibility factor to haze toxicity. This study will reveal whether GSTM1 deficiency aggravates haze-induced acute airway inflammation and underlying mechanisms by means of panel study and the in vitro model of primary human bronchial epithelial cells with GSTM1 null genotype. In the panel study, the subjects with GSTM1 positive and null genotypes will be examined 6 times using sputum induction for acute airway inflammatory responses under different haze conditions, followed by statistical analysis to specify whether GSTM1 deficiency could facilitate haze-induced airway inflammation. In addition to verifying the key results from the panel study the in vitro study will also elucidate which inflammatory signaling pathways can be modified by GSTM1 deficiency in the promotion of haze-induced airway inflammation.