摘要:
为了探究不同暴露时间甲醛对小鼠哮喘模型肺氧化应激及IL-17表达的影响,用浓度为3.0 mg·m-3的甲醛气体吸入染毒,同时将48只雄性Balb/c小鼠随机分为6组:(1)对照组(生理盐水组);(2)ovalbumin(OVA)致敏组;(3)0.5 h甲醛+OVA组;(4)1 h甲醛+OVA组;(5)1.5 h甲醛+OVA组;(6)2 h甲醛+OVA组,以不同时间长度进行甲醛暴露,连续35 d。OVA致敏组、0.5 h甲醛+OVA组、1 h甲醛+OVA组、1.5 h甲醛+OVA组、2 h甲醛+OVA组均在第11、18及25天腹腔注射OVA致敏液(5 mg OVA+175 mg Al(OH)3+30 mL生理盐水),第29~35天(共计1周)进行1% OVA雾化(30 min·d-1),每日1次,诱发哮喘。第36天进行以下操作:取肺组织测定肺系数并制作肺匀浆,检测肺组织中活性氧自由基(ROS)、丙二醛(MDA)和还原型谷胱甘肽(GSH)的含量,并采用ELISA法检测肺组织中IL-17的水平。同时,采用HE染色法观察小鼠肺部气道的病理学变化。结果显示,在浓度为3.0 mg·m-3的甲醛气体吸入染毒条件下,与对照组相比,1.5 h甲醛+OVA染毒组、2 h甲醛+OVA染毒组ROS、MDA、IL-17含量上升,具有统计学意义(P<0.01)。同时,随着暴露时间长度的增加,小鼠肺部气道出现明显病理学变化。综上所述,每天2 h甲醛+OVA染毒能对小鼠肺造成损伤并恶化OVA对小鼠肺的损伤,产生炎症反应,并通过氧化应激反应介导。
Abstract:
In this study, an ovalbumin (OVA)-sensitized mice asthma model was established to investigate the effect of different exposure duration of 3.0 mg·m-3 formaldehyde (FA) in pulmonary oxidative stress and IL-17 expression. 48 male Balb/c mice were randomly divided into 6 groups: (1) saline control group, (2) OVA-sensitized group, (3) OVA-combined with 0.5 h FA group, (4) OVA-combined with 1 h FA group, (5) OVA-combined with 1.5 h FA group, (6) OVA-combined with 2 h FA group. The mouse asthma model was developed by OVA sensitization and challenge. The mice were inhaled with different exposure duration of 3.0 mg·m-3 FA from day 1 to 35 and were sensitized with OVA+Al(OH)3 (5 mg OVA and 175 mg Al(OH)3 in 30 mL saline each time) or saline (30 mL saline each time) by intraperitoneal injection on day 11, 18 and 25. This was then followed by an aerosol challenge in 1% OVA (30 min·d-1) from day 29 to 35 (7 times) using an ultrasonic nebulizer. On the 36th day, the organ coefficient of mice lung was counted, then the contents of reactive oxygen species (ROS), glutathione (GSH) and malondialdehyde (MDA) of mice lung were measured, and the concentrations of interleukin-17 (IL-17A) were detected by using ELISA. Pulmonary histopathological examination was also conducted. The results showed that compared with control group, the OVA-combined with 1.5 h FA group and OVA-combined with 2 h FA group increased ROS, MDA and IL-17A contents significantly (P<0.01). The results of IL-17 and oxidative stress biomarkers (ROS, GSH and MDA contents) as well as histopathological examination supported the notion that long time (>1.5 h) exposure of 3.0 mg·m-3 FA may promote and aggravate allergic asthma. Increased ROS, GSH and MDA contents in this mouse model suggested that oxidative stress might be one of the molecular mechanisms of the aggravation effect induced by FA.