PM2.5暴露对哮喘大鼠气道形态及FOXP3基因DNA启动子区甲基化影响的实验研究  

Effects of PM2.5 on Airway Morphology and DNA Promoter Methylation of FOXP3 Gene in Asthmatic Rats

作　　者：林秀山 周向东[1] 王才春[1] LIN Xiushan;ZHOU Xiangdong;WANG Caichun(Department of Respiratory Medicine,the First Affiliated Hospital of Hainan Medical college,Haikou 570102,China)

机构地区：[1]海南医学院第一附属医院呼吸内科,海口570102

出　　处：《实验动物科学》2020年第1期54-58,共5页Laboratory Animal Science

基　　金：海南医学院第一附属医院2017年度青年培育基金(No.HYFYPY201705)。

摘　　要：目的探讨PM2.5暴露对哮喘大鼠气道形态及FOXP3基因DNA启动子区甲基化的影响。方法选择50只SD大鼠,随机选择10只作为空白对照组,40只采用卵清蛋白激发、致敏构建哮喘模型,并根据PM2.5干预剂量的不同,进一步分为单纯哮喘组、低剂量组、中剂量组、高剂量组,比较不同剂量PM2.5对哮喘大鼠的病程进展影响。结果(1)与对照组及单纯哮喘组相比,所有PM2.5干预组大鼠的体质量均明显较低(P<0.05),且左肺指数及心脏指数也显著较高(P<0.05),但脾脏指数无明显差异(P>0.05)。(2)与对照组相比,哮喘组肺泡灌洗液内细胞总数升高最显著,低、中剂量干预组也明显升高,但高剂量干预组无明显变化(P>0.05)。与对照组及哮喘组比较,随着PM2.5干预剂量的升高,大鼠BALF内的嗜酸性粒细胞、中性粒细胞、淋巴细胞计数也呈逐渐上升趋势,巨噬细胞呈逐渐下降趋势,差异均具有统计学意义(P<0.05)。(3)对照组、哮喘组、低剂量组、中剂量组、高中剂量组的FOXP3基因DNA启动子区的甲基化水平分别为(7.24±0.91)、(5.04±3.08)、(1.87±1.46)、(1.57±0.64)、(2.04±1.14),FOXP3 mRNA相对表达量分别为(1.02±0.18)、(0.81±0.19)、(0.62±0.15)、(0.53±0.14)、(0.32±0.04),随着PM2.5干预剂量的提高,大鼠的FOXP3基因DNA启动子区的甲基化水平及FOXP3 mRNA相对表达量均逐渐降低。结论PM 2.5对哮喘大鼠的损伤有一定的剂量依赖性,这可能与调低FOXP3基因DNA启动子区甲基化水平及FOXP3 mRNA相对表达量有关。Objective To investigate the effects of PM2.5 exposure on airway morphology and DNA promoter methylation of FOXP3 gene in asthmatic rats.Method 50 SD rats,10 control rats and 40 asthmatic rats were selected.According to the different doses of PM2.5,they were further divided into simple asthma group,low-dose group,medium-dose group and high-dose group.The effects of different doses of PM2.5 on the course of asthma in rats were compared.Result(1)Compared with the control group and asthma group,the weight of rats in all intervention groups was significantly lower(P<0.05),and the left lung index and heart index were also significantly higher(P<0.05).(2)Compared with the control group,the total number of cells in bronchoalveolar lavage fluid in asthma group increased most significantly,and that in low and medium dose intervention groups also increased significantly,but there was no significant change in high dose intervention group(P>0.05).Compared with the control group and asthma group,with the increase of PM2.5 intervention dose,the eosinophil,neutrophil and lymphocyte counts in BALF of rats also showed an upward trend,while macrophages showed a downward trend(P<0.05).(3)With the increase of the intervention dose,the methylation level and the relative expression of mRNA in the five groups decreased gradually.Conclusion PM2.5 can decrease the methylation level of DNA promoter region and the relative expression of FOXP3 gene.

关 键 词：哮喘 PM2.5 叉状头/翅膀状螺旋转录因子 

分 类 号：R12[医药卫生—环境卫生学]