Effects of Combined Exposure to Formaldehyde and PM2.5 on the Brain of Balb/c Mice Asthma Model

摘要

Epidemiological studies have shown that there is a link between asthma and brain damage, but toxicological studies have not fully confirmed yet, especially the effects of asthma on the brain. In this sωdy， at first， we explore the effects of asthma on the brain through the establishment of an allergic asthma model. Then PM_(2.5), a typical outdoor air pollutant and formaldehyde, a typical indoor air pollutant were selected to be closer to the true environment and find whether there is any synergism between them. In this study, an ovalbumin (OVA)-sensitized mice asthma model was established. 30 male Balb/c mice were randomly divided into 5 groups: (1) saline control group, (2) OVA-sensitized group, (3) OVA-combined with formaldehyde exposure group, (4) OVA-combined with PM_(2.5) exposure group， (5) Combination of OVA, formaldehyde and PM_(2.5) exposure group. The mice were inhaled with formaldehyde or/and instilled with PM_(2.5) from day 1 to 18. The mice asthma model was developed by OVA sensitization and challenge. The mice 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 1, 7 and 14. This was then followed by an aerosol challenge in 1% OVA (30 min. d~(-1) from day 19 to 25 (7 times) using an ultrasonic nebulizer. On the 26th day, the organ coefficient of mice brain was counted, then the contents of oxidative stress of mice brain were measured, including reactive oxygen species' (ROS), glutathione (GSH) and malondialdehyde (MDA), and the concentrations of NF-kB and interleukin-1? (IL-1β) were detected by using ELISA kits. Detection of interleukin-6 (IL-6) was made with immunohistochemical method. Histological assay for brain was also conducted. In our results, all the OVA treated groups showed a significant increase of ROS and a significant decrease of GSH contents when compared with the control group. Except OVA-sensitized group, other OVA treated groups also showed a significant increase of MDA contents when compared with the control group, and MDA contents of OVA-sensitized group showed significant change when compared to the combined exposure group. In ROS and GSH， combined exposure showed some joint effect compared with single exposure. When OVA was applied in combination with formaldehyde and PM_(2.5), NF-kB was activated. And all the OVA treated groups showed increased levels of IL-l ? and IL-6 compared with the control group. And the combined exposure showed an aggravated effect when compared with OVA-sensitized group. Histopathological observation of the hippocampus in mice brain clearly showed the difference of eosin (EO) stained neurons in the combined exposure group compared with the control group and OVA-sensitized group. The pyramidal neurons of the mice with allergic asthma exposed to formaldehyde and/or PM_(2.5) had been reduced in number, the cells were swollen and the dendrites had disappeared. Allergic asthma can cause damage to the brain through oxidative stress. Exposure to formaldehyde and PM_(2.5) will increase the damage caused by allergic asthma to the brain, which may be mediated by oxidative stress and NF-kB activation. This promotes the release of the inflammatory factors, resulting in increased inflammation.