| Background:Influenza is the world’s most common disease.Influenza virus induces an inflammatory response in the respiratory tract after infection,causing various complications such as viral pneumonia and even myocarditis,and even death.Clinical studies have found that people with low immunity are the main susceptible people to influenza viruses,and they also show more severe clinical symptoms after infection.At present,with the increase of social pressure,the number of patients with depression is increasing.The World Health Organization believes that depression is becoming the second largest disease in the world,and patients with depression have also shown the characteristics of low immunity in many studies.Therefore,it is important to study the immune effect of patients with depression on influenza virus infection.Aim:The main purpose of this article is to study the influence of depression on the inflammatory response of influenza virus infection and to explore its main influence mechanism,so as to provide targets and references for the development and research of new drugs.Method:This article uses the chronic restraint stress model(chronic restraint stress,CRS)to simulate the formation of stress depression.The mice are divided into normal group,stress group,normal infection group,and stress infection group.The alveoli are analyzed by flow cytometry The proportion of cells in the lavage fluid was changed,the lung tissue HE staining was used to observe the pathological changes of the lungs,and the real-time fluorescent quantitative PCR was used to study the changes of cytokines.GC-MS detects the changes of metabolites in mouse serum.ChIP experiment observes mouse epigenetics.Results:Through research,it was found that the stressed mice showed a stronger inflammatory response after influenza virus infection.At the same time,we observed the difference between the stressed mice and normal mice after the infection after the alveolar macrophages were cleared.Disappeared,indicating that alveolar macrophages played a key role in it.Testing the function of alveolar macrophages in mice found that the apoptosis of alveolar macrophages in the stress group after infection was more than that of the normal infection group,and the mitochondrial function also received more damage than the normal infection group.Increased production of active oxygen.The level of oxidative phosphorylation decreased significantly.ATP production is reduced.Using metabonomics to detect the metabolites of the mitochondrial tricarboxylic acid cycle,it was found that the α-ketoglutarate in the stressed mice was significantly lower than that in the normal group.α-ketoglutarate,as the reaction substrate of methylase,would Obviously affect mice.Simultaneously stressed mice have a significantly higher methylation level of alveolar macrophages than normal mice.At the same time,the methylation levels of the dryness factors KLF4 and KLF2 increase,and the hydroxymethylation level decreases.After supplementing withα-ketoglutarate,there was no significant difference between normal mice and stressed mice after infection.Conclusion:Stress can affect the function of mouse mitochondria,leading to the content of α-ketoglutarate in mice,leading to increased methylation levels of alveolar macrophages,and increased methylation levels of dry factors KLF4 and KLF2,which affect alveolar macrophages Self-renew of cells;at the same time,it causes alveolar macrophages to be more prone to apoptosis and weaken their proliferation ability.Causes stress in mice after influenza virus infection.Shows a higher viral load and a more severe inflammatory response. |
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