Effects Of Combined Ambient Temperature And Nitrogen Dioxide On Allergic Asthma And Its Mechanisms

Objective:The impact of climate change and air pollution on human health has become the focus of scientific research.Therefore,this study explored the effects of ambient temperature and nitrogen dioxide exposure on allergic asthma and its mechanism to provide new ideas for the development and clinical treatment of allergic asthma drugs.Methods:The Balb/c male mice were exposed to five different environments:low temperature（10℃）,normal temperature（24℃）,high temperature（35℃）,nitrogen dioxide（NO₂）,high temperature and NO₂compound exposure（35℃+NO₂）.To study its mechanism,the group of compound exposure was added blocker capsazepine.The exposure time of NO₂ and temperature was 30 days for 4 hours each day.From day 14,mice were sensitized by intraperitoneal injection of ovalbumin and Al（OH）₃every three days.Ovalbumin solution was challenged for 30 minutes from day 32 to 38,while the control group was treated with saline.After the final challenge,on the one hand,7 mice in each group were selected to measure the pulmonary function of inspiratory resistance（Ri）,expiratory resistance（Re）and airway compliance（Cldyn）;On the other hand,8 mice were selected to assess the serum protein,lung function and pulmonary inflammation.The count of inflammatory cells was measured by a blood cell analyzer;Serum immunoglobulin（Total- E,OVA-s E）,DNA oxidative damage 8-OHdG,Th1/Th2 cytokines（IL-4,IFN-γ）,oxidative stress（ROS,MDA,GSH）were measured by ELISA method;Lung histopathological analysis;Inflammatory factors（IL-6,TNF-α）and the expression of TRPs（TRPV1,TRPM8,TRPA1）were measured by immunohistochemical method.Results:A mouse model of asthma was adopted in our experiment.Compared with the control group,the inflammatory cell count,Total- E,OVA-s E,8-OHdG,IL-4,IL-6,TNF-α,ROS,MDA,and airway resistance were significantly increased,while IFN-γ,GSH and airway compliance were significantly decreased.Lung tissue structure was changed obviously with more inflammatory cell infiltration,goblet cells proliferation and pulmonary fibrosis.Compared with OVA-sensitized group,the serum levels of immune proteins in low temperature group,high temperature group,NO₂ group and high temperature and NO₂ combined exposure group were significantly increased,the proinflammatory factors and oxidative stress indicators were significantly increased,while the airway hyperresponsiveness was aggravated.Pathological sections showed airway wall thickening,mucus hypersecretion and subepithelial fibrotic hyperplasia around the airway.TRPA1 in the low temperature group and TRPV1 in the high temperature group were significantly upregulated.The results showed that low temperature,high temperature,NO₂ and high temperature and NO₂ combined exposure could aggravate asthma-like lesions in mice and the effect of high temperature was more significant,However,there was no synergistic effect between high temperature and NO₂.After adding the blocker capsazepine,the airway inflammatory was reduced significantly.Conclusion:In this experiment,by constructing a mouse asthma disease model and studying the molecular mechanism under different environmental exposures,the results show that:（1）High/Low temperature and NO₂ exposure alone can promote the airway inflammatory response of allergic asthma;（2）The combined exposure of high temperature and NO₂can further aggravate physiological and biochemical indicators of asthma,but there is no significant synergistic effect between high temperature and NO₂;（3）Oxidative stress and TRP ion pathway play an important role in the development of allergic asthma,the capsazepine blocker could reduce the levels of not only oxidative stress,but also the expression of TRPV1.