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 study,at first,we e...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 study,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 m L saline each time) or saline( 30 m L 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 26 th 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-κB and interleukin-1β( 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-κB was activated. And all the OVA treated groups showed increased levels of IL-1β 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-κB activation.This promotes the release of the inflammatory factors,resulting in increased inflammation.展开更多
By detecting the influence of six main ingredients of PM2.5 mineral dusts on the A549 cell morphology, proliferation inhibition rate, micronuclei and DNA damage, to explore the genotoxicity of PM2.5 mineral dusts. (1)...By detecting the influence of six main ingredients of PM2.5 mineral dusts on the A549 cell morphology, proliferation inhibition rate, micronuclei and DNA damage, to explore the genotoxicity of PM2.5 mineral dusts. (1) After exposure to six kinds of dusts of 200 μg/mL concentration for 24 hours, the morphology of A549 cells were observed using Wright-Giemsa staining. (2) After exposure to different concentrations of mineral dusts for 24 hours, the proliferation inhibition rate of A549 cells was detected by MTT assay. (3) Cells were exposed to PM2.5 mineral dusts at a concentration of 200 μg/mL for 24 h. After Wright-Giemsa staining, the rates of micronucleus cells were counted under oil microscope. (4) Observe Comet phenomenon by SCGE electrophoresis, the degree of DNA damage was observed by OTM. (1) Compared to the control group, membrane destruction, nuclear pyknosis and mineral surface adhesion were mainly seen in the Sericite group and Albite group. In the Quartz group and Montmorillonite group, enlarged cell gaps, loosely arranged cells, absorption of a large number of minerals on the cell surface, and cell pyknosis were observed. (2) The proliferation inhibition rate of the six kinds of dusts to A549 cells were (from large to small): KWC-M>Nano-SiO2>KWC-S>KWC-Q>KWC-A>KWC-C.The dust concentration was positively related to the inhibition of cell proliferation rate. (3) With the dusts concentration increased, the incidence of micronuclei gradually increased. The rate was positively correlated to exposure concentration. (4) The six mineral dusts can damage DNA of the A549 cells by dose-response relationship.The higher concentration of the mineral dusts, the more obvious of the DNA damagenation. There’s statistically significant compared with the control group. The six main ingredients of the PM2.5 mineral dusts can change A549 cell morphology from varying degrees, improve proliferation inhibition rate of the cells, increase the number of micronuclei cells, damage DNA.Then we come to the conclusion that PM2.5 mineral dusts can change the genotoxicity of the cells.展开更多
基金National Natural Science Foundation of China (No: 21577045).
文摘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 study,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 m L saline each time) or saline( 30 m L 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 26 th 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-κB and interleukin-1β( 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-κB was activated. And all the OVA treated groups showed increased levels of IL-1β 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-κB activation.This promotes the release of the inflammatory factors,resulting in increased inflammation.
基金Project supported by the State Key Program of National Natural Science of China(No.41130746)
文摘By detecting the influence of six main ingredients of PM2.5 mineral dusts on the A549 cell morphology, proliferation inhibition rate, micronuclei and DNA damage, to explore the genotoxicity of PM2.5 mineral dusts. (1) After exposure to six kinds of dusts of 200 μg/mL concentration for 24 hours, the morphology of A549 cells were observed using Wright-Giemsa staining. (2) After exposure to different concentrations of mineral dusts for 24 hours, the proliferation inhibition rate of A549 cells was detected by MTT assay. (3) Cells were exposed to PM2.5 mineral dusts at a concentration of 200 μg/mL for 24 h. After Wright-Giemsa staining, the rates of micronucleus cells were counted under oil microscope. (4) Observe Comet phenomenon by SCGE electrophoresis, the degree of DNA damage was observed by OTM. (1) Compared to the control group, membrane destruction, nuclear pyknosis and mineral surface adhesion were mainly seen in the Sericite group and Albite group. In the Quartz group and Montmorillonite group, enlarged cell gaps, loosely arranged cells, absorption of a large number of minerals on the cell surface, and cell pyknosis were observed. (2) The proliferation inhibition rate of the six kinds of dusts to A549 cells were (from large to small): KWC-M>Nano-SiO2>KWC-S>KWC-Q>KWC-A>KWC-C.The dust concentration was positively related to the inhibition of cell proliferation rate. (3) With the dusts concentration increased, the incidence of micronuclei gradually increased. The rate was positively correlated to exposure concentration. (4) The six mineral dusts can damage DNA of the A549 cells by dose-response relationship.The higher concentration of the mineral dusts, the more obvious of the DNA damagenation. There’s statistically significant compared with the control group. The six main ingredients of the PM2.5 mineral dusts can change A549 cell morphology from varying degrees, improve proliferation inhibition rate of the cells, increase the number of micronuclei cells, damage DNA.Then we come to the conclusion that PM2.5 mineral dusts can change the genotoxicity of the cells.
