PM_(2.5)和甲醛联合暴露致小鼠肺损伤及其分子机制的研究

Study on the Lung Damage in Mice Induced by a Combined Exposure of PM_(2.5) and Formaldehyde and its Molecular Mechanism

我国城市当前普遍存在室外大气PM_(2.5)与室内甲醛(FA)联合污染状况,二者均被报道在单独暴露下可以导致肺损伤并诱导和诱发哮喘的急性发作,但其联合污染的具体效应,以及分子机制目前尚不清楚。为探究PM_(2.5)和/或甲醛暴露对小鼠的肺损伤及其可能的机制,分别将雄性Balb/c小鼠分为以下6组:对照组,AZD8055组,PM_(2.5)组,FA组,PM_(2.5)+FA组,PM_(2.5)+FA+AZD8055组。染毒结束后,观察肺组织病理学变化;检测肺组织氧化损伤,活性氧(reactive oxygen species,ROS),还原型谷胱甘肽(glutathione,GSH)和丙二醛(malondialdehyde,MDA)的含量,DNA损伤,DNA-蛋白质交联(DNA-protein crosslink,DPC)系数和8羟基脱氧鸟苷(8-OH-d G)的含量,以及细胞凋亡、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)的含量。结果表明,当吸入气态甲醛浓度为3 mg·m-3,气道滴注PM_(2.5)浓度为2.5 mg·m L-1时,肺组织出现不同程度的支气管重塑和炎症细胞浸润。ROS显著上升,GSH显著下降,DPC、8-OH-d G以及Caspase-3都显著上升。添加AZD8055后,肺组织损伤效应更加显著。PM_(2.5)复合甲醛的暴露导致小鼠肺损伤具有协同作用,氧化应激及其下游的DNA损伤可能是甲醛联合PM_(2.5)致小鼠肺损伤的一种重要机制。

Currently, the combined pollution of PM2.5 and indoor formaldehyde（FA） has become a common issue in main cities of China. The two pollutants have both been reported to induce the lung damage and worsen allergic asthma, while there is no knowledge that whether their combined exposure has synergistically toxicological effects and its molecular mechanisms remain unknown. In order to explore the influence and the underlying mechanisms of FA and PM2.5 on lung damage, male Balb/c mice were randomly divided into six groups： Control group,AZD8055 group, PM2.5 group, FA group, PM2.5＋FA group, PM2.5＋FA＋AZD8055 group. After the end of treatment,histopathological changes of lung tissue were observed, furtherly the oxidative damage（ROS, GSH, MDA）, DNAdamage（DPC, 8-OH-d G） and apoptosis（Caspase-3） in lung tissue were detected. The results showed that compared with control group, different degrees of pathological changes in the lung tissue when exposed to 3 mg·m-3 formaldehyde and 2.5 mg·m L-1 PM2.5. The level of ROS were significantly increased, GSH content were significantly decreased, and the levels of DPC, 8-OH-d G and caspase-3 were also significantly increased. These adverse effects were more potent with the concurrent administration of AZD8055. In short, co-exposure to FA and PM2.5 has synergistic effects on lung damage and oxidative stress along with its downstream DNA damage may be one of important mechanisms accounting for the lung injury in mice caused by combined exposure.