Changes In The Expression Of PGE2/EP Signaling Pathway In Lung Tissues Of COPD Caused By Vehicle Exhaust Exposure

【Background】The common causes of chronic obstructive pulmonary disease(COPD)are smoking,air pollution,etc.,which are mainly manifested as repeated coughing,sputum production,and difficulty breathing.It is a form of airflow limitation that cannot be completely reversed,chronic inflammation,and emphysema.Characteristic chronic lung disease.According to data from the Global Burden of Disease Research Team,COPD has become the fourth leading cause of death in the world,and over time,the number of deaths from COPD may further increase.The pathogenesis of COPD is currently believed to be mainly related to chronic inflammation,oxidative stress and protease-antiprotease imbalance caused by airway wall and alveolar septal remodeling,and lung tissue structure destruction,and inflammation plays a major role in it.It is generally believed that the release of motor vehicle exhaust(MVE)is an important part of air pollution.Establishing an animal model that conforms to the law of clinical disease occurrence and development and pathophysiological basis is an important basis for studying the pathogenesis of COPD caused by motor vehicle exhaust.Prostaglandin E2(PGE2)is a metabolite of arachidonic acid in the vascular endothelium and works by binding to EP.EP is a transmembrane protein on the cell membrane.It belongs to the G protein receptor superfamily and is divided into EP1,EP2,EP3,EP4 Four subtypes.PGE2 plays different roles by binding to different subtypes of EP receptors.Each EP subtype has different signal transduction characteristics.Among them,the EP1 receptor can increase the intracellular Ca2+concentration,thereby activating phosphocreatine kinase C(PLC)to mediate signal transmission.EP2 and EP4 receptors enhance the activity of adenylate cyclase by binding to protein G,increase the content of cyclic adenosine monophosphate(c AMP),and increase the activity of protein kinase A.EP3 reduces the activity of adenylate cyclase by binding to a variety of G proteins.In addition,EP receptors also interfere with each other.A large number of studies have shown that EP1,EP2,and EP4 can interact with epidermal growth factor,which adds to the diversity and complexity of PGE2/EP signaling.A number of studies have shown that PM2.5 is an important factor in the pathogenesis of COPD,it can induce the release of cytokines and the increase of airway inflammation.As an important inflammatory factor,does PGE2 change its expression in COPD caused by PM2.5.The purpose of this study is to observe the role of PGE2/EP in the pathogenesis of COPD.【Objectives】By constructing a rat model of COPD caused by long-term motor vehicle exhaust gas exposure,observe the expression changes of the PGE2/EP signaling pathway during the occurrence and development of COPD caused by long-term motor vehicle exhaust gas exposure,and understand the role of PGE2 and different EP receptors.The role of airway chronic inflammation,to further understand the occurrence and outcome of airway inflammation,to improve the pathogenesis of COPD and provide a new entry point for the prevention and treatment of COPD.【Methods】This study is divided into three parts:(1)First,we use the method of long-term exposure to motor vehicle exhaust to build a COPD rat model.After the modeling is completed,the rats are evaluated in various aspects,including lung function and lung.Emphysema,small airway remodeling,airway inflammation,etc.;(2)Observe the effect of the PGE2/EP signaling pathway in the COPD model rats prepared under the locomotive exhaust factor,and then observe the changes of PGE2 and other inflammatory factors in the experimental model;(3)Finally,at the cellular level,detect the effects of long-term locomotive exhaust standard stimulation on the PGE2/EP signaling pathway and changes in related inflammatory factors.【Results】1.The COPD rat model was successfully constructed after 6 months of exposure to motor vehicle exhaust: it showed decreased lung function,increased airway inflammation,emphysema,airway goblet cell hyperplasia and other pathological changes.2.Compared with the normal control group,the expression of PGE2 and EP1/EP4 in the lung tissue of the COPD rat model increased,but the expression of EP2/EP3 did not change significantly.3.Compared with the normal control group,long-term exposure to PM2.5 leads to an increase in the expression of PGE2 and EP1/EP4 in airway epithelial cells(BEAS-2B cell),and has no obvious effect on EP2/EP3.【Conclusion】Using the method of vehicle exhaust exposure,an animal model of COPD was successfully constructed.Motor vehicle exhaust exposure can up-regulate the expression level of EP1/EP4 in the lung tissues of model animals and experimental cells,but has no obvious effect on EP2/EP3.PGE2 may play a regulatory role in the development of COPD induced by vehicle exhaust by combining with EP1/EP4.