| Vehicle emission has been the predomina nt contribution to air pollution in major cities in C hina.PM2.5 is an important air pollutant.In traffic related air pollutants,PM2.5 mainly comes from exhaust gas from diesel vehicles.Epidemiological studies have shown that traffic related air pollution is closely related to the prevalence of cough.Studies have shown that the TRPA1 in vagus nerve and airway can be activated by air pollutants such as diesel exhaust,which leads to a series of respiratory diseases.However,the mechanisms of air polluta nts induce cough are not yet clear,and the relationship between air pollutants and cough sensitivity is rarely reported.In our previous studies of outdoor exposure,we demonstrated that traffic related air pollution can induce cough hypersensitivity in guinea pigs.However,there are a lot of interference factors in outdoor exposure,the exposure environment is uncontrollable and unstable.Therefore,it is necessary to establish a controllable and stable indoor pollutant exposure test to further investigate the relationship between air pollutants and cough sensitivity.Thus,this study constructed a controllable and stable diesel exhaust indoor environmental exposure,observating the relationship of diesel exhaust pollutants and cough sensitivity in guinea pigs,investigating the role of TRPA1 in diesel exhaust pollution impacting cough sensitivity in guinea pigs.Objective: To establish a controllable and stable model of cough hypersensitivity induced by diesel exhaust exposure in guinea pigs and to explore its mechanism.Methods:1.Grouping of animals: The animals were divided into control group,low concentration exhaust gas exposure group,high concentration exhaust gas exposure group,low concentration exhaust gas exposure +HC-030031 group,high concentration exhaust gas exposure HC-030031 group.2.Establish indoor exposure environment: guinea pigs in exposed groups were exposed to diesel exhaust pollutants for 3 hours every day for 14 consecutive days.The target concentration of PM2.5 was 200 μg/m3 in low concentration exhaust gas exposure group and low concentration exhaust gas exposure + HC-030031 group.The target concentration of PM2.5 was 1000 μg/m3 in high concentration exhaust gas exposure group and high concentration exhaust gas exposure + HC-030031 group.The guinea pigs in the control group were kept in relatively clean animals house.3.Pharmacological intervention: low concentration exhaust pollutants exposure +HC-030031 group and high concentration exhaust pollutants exposure HC-030031 group were received HC-030031(200mg/kg,ip)once daily.Drugs were administrated to guinea pig everyday before exposure and the last administration was performed 2 hours before cough reflex sensitivity test.4.Bronchial airway lavage fluid and airway tissue were harvested 12 hours after the cough reflex sensitivity test.BALF cell differential and airway histomorphology study were performed.The concentration of substance P in lung tissue was quantified using ELISA kit method.The TRPA1 content in lung tissue and vagal gangliac were detected using Western Blot analysis.Results: 1.The exposure of diesel exhaust gas could shorten the cough latency and increase the number of cough provocation frequency in guinea pigs,and the effect became more obvious with the increase of tail gas concentration.HC-030031 can prolong the cough latency and reduce the number of cough provocation frequency to some extent.2.After diesel exhaust gas exposure,the total number of BALF cells increased,and increased with the increase of exhaust gas concentration.Diesel exhaust exposure can induce airway inflammation in guinea pigs,neutrophils and eosinophils are the main inflammatory cells.The proportion of inflammatory cells increases with the increase of tail gas concentration.HC-030031 can decrease the total number of cells,neutrophils and eosinophils.3.After exposure to diesel exhaust,the lung tissues of the exposed group showed varying degrees of vascular / peripheral inflammation,tissue edema,and bronchial epithelial detachment.HC-030031 can suppress this effect to some extent.4.After exposure to diesel exhaust gas,the SP content in lung tissue increased,and increased with the increase of exposure concentration.HC-030031 could reduce the content of SP in lung tissue.5.After diesel exhaust gas exposure,the TRPA1 content of lung tissue and vagal ganglia increased in different degrees.In the two vagal ganglia,the content of TRPA1 increased mainly in jugular ganglion.HC-030031 can reduce the TRPA1 content in lung tissue and vagal ganglia.Conclusion: 1.The indoor exposure environment of diesel exhaust can induce cough hypersensitivity and airway inflammation in guinea pigs.The exposure method is controllable and stable,and can be used as an animal model for study of cough hypersensitivity.2.Diesel exhaust pollutants can induce nonspecific airway inflammation in guinea pigs,mainly with neutrophils and eosinophils,and produce neurogenic inflammation at the same time.3.Diesel exhaust pollutants can induce cough hypersensitivity in guinea pigs,which is related to the activation of TRPA1 in vagal sensory nerve and airway. |
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