低浓度甲醛和PM2.5联合暴露对哮喘小鼠的影响

为探究低浓度甲醛（FA）单独及与PM_2.5联合暴露对哮喘小鼠的影响，选取70只雄性Balb/c小鼠，随机分为5组，分别为：对照组、卵清蛋白（OVA）组、FA+OVA组、PM_2.5+OVA组、FA+PM_2.5+OVA组，每组14只，其中6只进行气道高反应性（AHR）检测，其余8只用于检测血清T-IgE、肺泡灌洗液（BALF）中IFN-γ、IL-4以及肺组织中活性氧（ROS）、丙二醛（MDA）的含量，并对BALF中炎症细胞进行计数.同时对小鼠肺组织进行H&E染色以及p-p38MAPK和p-p65NF-κB免疫组化分析.结果显示，与OVA组相比，0.5mg/m³FA单独暴露组哮喘小鼠肺部MDA水平显著升高（P<0.001），肺部炎症细胞呈现上升趋势（P>0.05），0.5mg/m³FA和0.5mg/kg PM_2.5联合暴露组哮喘小鼠肺部炎症显著加重（P<0.05或P<0.01），肺功能减弱（P<0.01），肺部氧化应激水平以及p38MAPK和NF-κB的磷酸化水平均显著升高（P<0.05或P<0.001），Th2型细胞因子释放显著增加（P<0.01）.因此，低浓度FA单独暴露会加重哮喘小鼠肺部损伤而非抑制，并且可进一步促进PM_2.5对哮喘小鼠肺部的损伤，即低浓度FA和PM_2.5联合暴露会对哮喘小鼠肺部造成严重损害，这可能与ROS介导的p38MAPK途径加剧Th1/Th2型免疫反应失衡有关.

The effect of combined exposure of low concentration formaldehyde and PM2.5 on asthma model mice

In order to explore the effects of a combined exposure of formaldehyde (FA) and PM_2.5 with low concentration on the asthmatic mice, 70male Balb/c mice were randomly divided into 5groups:control group, OVA group, FA + OVA group, PM_2.5 + OVA group, FA + PM_2.5 + OVA group. Amongst 14mice in each group, 6were tested for airway hyper reactivity (AHR), and the remaining 8were detected for T-IgE in serum, as well as IFN-γ, IL-4in BALF, and ROS, MDA in lung tissue. Besides, the inflammatory cells in BALF were counted. In addition, H&E staining and immunohistochemical analysis of p-p38MAPK and p-p65NF-κ B were conducted with mice lung. A significant increase in the level of MDA (P<0.001), as well as a trend of increase in inflammatory lung cells(P>0.05) were demonstrated in asthmatic mice group exposed to 0.5mg/m³ FA alone. While in the group exposed to combined 0.5mg/m³ FA and 0.5mg/kg PM_2.5 with low concentration, a significant aggravation in lung inflammation(P<0.05, P<0.01) and attenuation in lung function(P<0.01) were observed. Significant increase was also found in the level of both oxidative stress and the phosphorylation of p38MAPK and NF-κ B in lung(P<0.05, P<0.001). In addition, the release of Th2 type cytokine was also enhanced significantly(P<0.01). Hence exposure to low-concentration FA alone could lead to the aggravation instead of inhibition of lung injury in asthmatic mice, and might further promote the damage to lungs in asthmatic mice caused by PM_2.5. In conclusion, combined exposure to FA and PM_2.5 with low concentration could lead to severe lung damage in asthmatic mice, with a possible correlation to the imbalance of Th1/Th2 type responses intensified by the ROS-mediated p38MAPK pathway.