| Asthma is a life-long non-infectious airway chronic inflammatory disease.It affects people of almost all ages,it not only seriously interferes with the patient's normal activities,but also seriously affects the quality of life.According to the WHO report,there are about 300 million asthmatic patients in the world,and it is expected to increase to 400 million by 2025.At the same time,about 250,000 people die prematurely every year due to asthma.Air pollution is the most serious public health problem faced by countries all over the world,it always appears in the form of a mixture,but epidemiological and animal studies tend to focus on the negative impacts of single air pollutant on health,while ignoring the impacts of the mixed pollution on health.One of the most typical outdoor air pollutants is PM2.5,which has become the largest air pollutant in China.Due to the prevalence of decoration pollution,formaldehyde has become a typical indoor air pollutant in China.PM2.5 and formaldehyde can not only increase the incidence of asthma,but also increase the existing asthma symptoms,which is very dangerous for asthma patients.In this study,the joint exposure to PM2.5 and formaldehyde was selected in order to get closer to the real environment,the aim is to explore the joint toxicity and the mechanism of the combined exposure on the OVA-sensitized Balb/c mice asthma model.We hope to attract attention to the toxicity of mixed pollutants,and to provide experimental basis for the prevention and control of asthma exacerbated by air pollution in the future.In order to investigate the effects of combined exposure to PM2.5 and formaldehyde on the allergic asthma model,we selected representative indicators for detection,including total serum immunoglobulin E(T-IgE)levels,mast cell degranulation in lung tissues,cytokine levels(IFN-?,IL-4,IL-5,IL-10,IL-17,TNF-?)and inflammatory cell counts(eosinophils,lymphocytes,neutrophils)in bronchoalveolar lavage fluid(BALF),histopathological sections and oxidative stress levels(ROS,GSH,MDA)in lung tissues.In addition,we examined the levels of TRPV1 ion channel-releasing neuropeptides(Substance P and CGRP)in lung tissues to investigate the toxic mechanism of combined exposure in mice allergic asthma model.At the same time,the role of TRPV1 ion channel in this toxic mechanism was surveyed by the application of Capsazepine(Cpz),which is a specific blocker of the TRPV1 ion channel.The experimental data showed that all OVA sensitized mice had significantly increased T-IgE concentrations,increased degranulation of mast cells in the lung,decreased IFN-?/IL-4 and IL-10/IL-17 ratios,increased secretion of TNF-? and IL-5.Th2 and Thl7 immune responses were raised.There were marked changes of oxidative stress levels in lung tissue,including increased contents of ROS,MDA and decreased contents of GSH.At the same time,the number of lymphocytes,eosinophils and neutrophils in BALF were increased,airway remodeling and collagen deposition were enhanced.In addition,the expressions of TRPV1,Substance P and CGRP were increased in lung tissue.The combination of PM2.5 and formaldehyde induced allergic asthma model group showed higher levels of oxidative stress,secretion of pro-inflammatory neuropeptides and enhanced the symptoms of allergic asthma in mice.The application of Cpz can effectively reduce the adverse effects of the combined exposure,including the decrease of the neurogenic inflammation,oxidative stress and injury in lung tissue,also decrease the symptoms of allergic asthma.This study showed that combined exposure to PM2.5 and formaldehyde can exacerbate lung injury in allergic asthma mice by exacerbating oxidative stress,inducing Thl/Th2 and Treg/Th17 immune imbalances,and neurogenic responses.The activation of the TRPV1 ion channel and the release of pro-inflammatory neuropeptides such as substance P and CGRP played an important role in the expansion of asthmatic inflammation.The specific antagonist Cpz can effectively reduce the damage. |
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